Bone marrow

Bone marrow is a semi-solid tissue which may be found within the spongy or cancellous portions of bones.[2] In birds and mammals, bone marrow is the primary site of new blood cell production or hematopoiesis.[3] It is composed of hematopoietic cells, marrow adipose tissue, and supportive stromal cells. In adult humans, bone marrow is primarily located in the ribs, vertebrae, sternum, and bones of the pelvis.[4] On average, bone marrow constitutes 4% of the total body mass of humans; in an adult having 65 kilograms of mass (143 lb), bone marrow typically accounts for approximately 2.6 kilograms (5.7 lb).[5]

Human marrow produces approximately 500 billion blood cells per day, which join the systemic circulation via permeable vasculature sinusoids within the medullary cavity.[6] All types of hematopoietic cells, including both myeloid and lymphoid lineages, are created in bone marrow; however, lymphoid cells must migrate to other lymphoid organs (e.g. thymus) in order to complete maturation.

Bone marrow transplants can be conducted to treat severe diseases of the bone marrow, including certain forms of cancer such as leukemia. Additionally, bone marrow stem cells have been successfully transformed into functional neural cells,[7] and can also potentially be used to treat illnesses such as inflammatory bowel disease.[8]

Bone Marrow
Details
SystemImmune system[1]
Identifiers
LatinMedulla ossium
MeSHD001853
TAA13.1.01.001
FMA9608
Anatomical terminology

Structure

The composition of marrow is dynamic, as the mixture of cellular and non-cellular components (connective tissue) shifts with age and in response to systemic factors. In humans, marrow is colloquially characterized as "red" or "yellow" marrow (Latin: medulla ossium rubra, Latin: medulla ossium flava, respectively) depending on the prevalence of hematopoetic cells vs fat cells. While the precise mechanisms underlying marrow regulation are not understood,[6] compositional changes occur according to stereotypical patterns.[9] For example, a newborn baby's bones exclusively contain hematopoietically active "red" marrow, and there is a progressive conversion towards "yellow" marrow with age. In adults, red marrow is found mainly in the central skeleton, such as the pelvis, sternum, cranium, ribs, vertebrae and scapulae, and variably found in the proximal epiphyseal ends of long bones such as the femur and humerus. In circumstances of chronic hypoxia, the body can convert yellow marrow back to red marrow to increase blood cell production.[10]

Hematopoietic components

Bone marrow WBC
Hematopoietic precursor cells: promyelocyte in the center, two metamyelocytes next to it and band cells from a bone marrow aspirate.

At the cellular level, the main functional component of bone marrow includes the progenitor cells which are destined to mature into blood and lymphoid cells. Marrow contains hematopoietic stem cells which give rise to the three classes of blood cells that are found in circulation: white blood cells (leukocytes), red blood cells (erythrocytes), and platelets (thrombocytes).[11]

Cellular constitution of the red bone marrow parenchyma[12]
Group Cell type Average
fraction
Reference
range
Myelopoietic
cells
Myeloblasts 0.9% 0.2–1.5
Promyelocytes 3.3% 2.1–4.1
Neutrophilic myelocytes 12.7% 8.2–15.7
Eosinophilic myelocytes 0.8% 0.2–1.3
Neutrophilic metamyelocytes 15.9% 9.6–24.6
Eosinophilic metamyelocytes 1.2% 0.4–2.2
Neutrophilic band cells 12.4% 9.5–15.3
Eosinophilic band cells 0.9% 0.2–2.4
Segmented neutrophils 7.4% 6.0–12.0
Segmented eosinophils 0.5% 0.0–1.3
Segmented basophils and mast cells 0.1% 0.0–0.2
Erythropoietic
cells
Pronormoblasts 0.6% 0.2–1.3
Basophilic normoblasts 1.4% 0.5–2.4
Polychromatic normoblasts 21.6% 17.9–29.2
Orthochromatic normoblast 2.0% 0.4–4.6
Other cell
types
Megakaryocytes < 0.1% 0.0-0.4
Plasma cells 1.3% 0.4-3.9
Reticular cells 0.3% 0.0-0.9
Lymphocytes 16.2% 11.1-23.2
Monocytes 0.3% 0.0-0.8

Stroma

The stroma of the bone marrow includes all tissue not directly involved in the marrow's primary function of hematopoiesis.[6] Stromal cells may be indirectly involved in hematopoiesis, providing a microenvironment that influences the function and differentiation of hematopoeietic cells. For instance, they generate colony stimulating factors, which have a significant effect on hematopoiesis. Cell types that constitute the bone marrow stroma include:

Function

Mesenchymal stem cells

The bone marrow stroma contains mesenchymal stem cells (MSCs),[11] also known as marrow stromal cells. These are multipotent stem cells that can differentiate into a variety of cell types. MSCs have been shown to differentiate, in vitro or in vivo, into osteoblasts, chondrocytes, myocytes, marrow adipocytes and beta-pancreatic islets cells.

Bone marrow barrier

The blood vessels of the bone marrow constitute a barrier, inhibiting immature blood cells from leaving the marrow. Only mature blood cells contain the membrane proteins, such as aquaporin and glycophorin, that are required to attach to and pass the blood vessel endothelium.[13] Hematopoietic stem cells may also cross the bone marrow barrier, and may thus be harvested from blood.

Lymphatic role

The red bone marrow is a key element of the lymphatic system, being one of the primary lymphoid organs that generate lymphocytes from immature hematopoietic progenitor cells.[14] The bone marrow and thymus constitute the primary lymphoid tissues involved in the production and early selection of lymphocytes. Furthermore, bone marrow performs a valve-like function to prevent the backflow of lymphatic fluid in the lymphatic system.

Compartmentalization

Biological compartmentalization is evident within the bone marrow, in that certain cell types tend to aggregate in specific areas. For instance, erythrocytes, macrophages, and their precursors tend to gather around blood vessels, while granulocytes gather at the borders of the bone marrow.[11]

As food

Animal bone marrow has been used in cuisine worldwide for millennia, such as the famed Milanese Ossobuco.

Clinical significance

Disease

The normal bone marrow architecture can be damaged or displaced by aplastic anemia, malignancies such as multiple myeloma, or infections such as tuberculosis, leading to a decrease in the production of blood cells and blood platelets. The bone marrow can also be affected by various forms of leukemia, which attacks its hematologic progenitor cells.[15] Furthermore, exposure to radiation or chemotherapy will kill many of the rapidly dividing cells of the bone marrow, and will therefore result in a depressed immune system. Many of the symptoms of radiation poisoning are due to damage sustained by the bone marrow cells.

To diagnose diseases involving the bone marrow, a bone marrow aspiration is sometimes performed. This typically involves using a hollow needle to acquire a sample of red bone marrow from the crest of the ilium under general or local anesthesia.[16]

Application of stem cells in therapeutics

Bone marrow derived stem cells have a wide array of application in regenerative medicine.[17]

Imaging

Medical imaging may provide a limited amount of information regarding bone marrow. Plain film x-rays pass through soft tissues such as marrow and do not provide visualization, although any changes in the structure of the associated bone may be detected.[18] CT imaging has somewhat better capacity for assessing the marrow cavity of bones, although with low sensitivity and specificity. For example, normal fatty "yellow" marrow in adult long bones is of low density (-30 to -100 Hounsfield units), between subcutaneous fat and soft tissue. Tissue with increased cellular composition, such as normal "red" marrow or cancer cells within the medullary cavity will measure variably higher in density.[19]

MRI is more sensitive and specific for assessing bone bone composition. MRI enables assessment of the average molecular composition of soft tissues, and thus provides information regarding the relative fat content of marrow. In adult humans, "yellow" fatty marrow is the dominant tissue in bones, particularly in the (peripheral) appendicular skeleton. Because fat molecules have a high T1-relaxivity, T1-weighted imaging sequences show "yellow" fatty marrow as bright (hyperintense). Furthermore, normal fatty marrow loses signal on fat-saturation sequences, in a similar pattern to subcutaneous fat.

When "yellow" fatty marrow becomes replaced by tissue with more cellular composition, this change is apparent as decreased brightness on T1-weighted sequences. Both normal "red" marrow and pathologic marrow lesions (such as cancer) are darker than "yellow" marrow on T1-weight sequences, although can often be distinguished by comparison with the MR signal intensity of adjacent soft tissues. Normal "red" marrow is typically equivalent or brighter than skeletal muscle or intervertebral disc on T1-weighted sequences.[20][9]

Fatty marrow change, the inverse of red marrow hyperplasia, can occur with normal aging,[21] though it can also be seen with certain treatments such as radiation therapy. Diffuse marrow T1 hypointensity without contrast enhancement or cortical discontinuity suggests red marrow conversion or myelofibrosis. Falsely normal marrow on T1 can be seen with diffuse multiple myeloma or leukemic infiltration when the water to fat ratio is not sufficiently altered, as may be seen with lower grade tumors or earlier in the disease process.[22]

Histology

Acute leukemia-ALL
A Wright's-stained bone marrow aspirate smear from a patient with leukemia.

Bone marrow examination is the pathologic analysis of samples of bone marrow obtained via biopsy and bone marrow aspiration. Bone marrow examination is used in the diagnosis of a number of conditions, including leukemia, multiple myeloma, anemia, and pancytopenia. The bone marrow produces the cellular elements of the blood, including platelets, red blood cells and white blood cells. While much information can be gleaned by testing the blood itself (drawn from a vein by phlebotomy), it is sometimes necessary to examine the source of the blood cells in the bone marrow to obtain more information on hematopoiesis; this is the role of bone marrow aspiration and biopsy.

The ratio between myeloid series and erythroid cells is relevant to bone marrow function, and also to diseases of the bone marrow and peripheral blood, such as leukemia and anemia. The normal myeloid-to-erythroid ratio is around 3:1; this ratio may increase in myelogenous leukemias, decrease in polycythemias, and reverse in cases of thalassemia.[23]

Donation and transplantation

Bone marrow biopsy
A bone marrow harvest in progress.
Site for procedure of Bone Marrow
The preferred sites for the procedure

In a bone marrow transplant, hematopoietic stem cells are removed from a person and infused into another person (allogenic) or into the same person at a later time (autologous). If the donor and recipient are compatible, these infused cells will then travel to the bone marrow and initiate blood cell production. Transplantation from one person to another is conducted for the treatment of severe bone marrow diseases, such as congenital defects, autoimmune diseases or malignancies. The patient's own marrow is first killed off with drugs or radiation, and then the new stem cells are introduced. Before radiation therapy or chemotherapy in cases of cancer, some of the patient's hematopoietic stem cells are sometimes harvested and later infused back when the therapy is finished to restore the immune system.[24]

Bone marrow stem cells can be induced to become neural cells to treat neurological illnesses,[7] and can also potentially be used for the treatment of other illnesses, such as inflammatory bowel disease.[8] In 2013, following a clinical trial, scientists proposed that bone marrow transplantation could be used to treat HIV in conjunction with antiretroviral drugs;[25][26] however, it was later found that HIV remained in the bodies of the test subjects.[27]

Harvesting

The stem cells are typically harvested directly from the red marrow in the iliac crest, often under general anesthesia. The procedure is minimally invasive and does not require stitches afterwards. Depending on the donor's health and reaction to the procedure, the actual harvesting can be an outpatient procedure, or can require 1–2 days of recovery in the hospital.[28]

Another option is to administer certain drugs that stimulate the release of stem cells from the bone marrow into circulating blood.[29] An intravenous catheter is inserted into the donor's arm, and the stem cells are then filtered out of the blood. This procedure is similar to that used in blood or platelet donation. In adults, bone marrow may also be taken from the sternum, while the tibia is often used when taking samples from infants.[16] In newborns, stem cells may be retrieved from the umbilical cord.[30]

Fossil record

Eusthenopteron BW
Bone marrow may have first evolved in Eusthenopteron, a species of prehistoric fish with close links to early tetrapods.

The earliest fossilised evidence of bone marrow was discovered in 2014 in Eusthenopteron, a lobe-finned fish which lived during the Devonian period approximately 370 million years ago.[31] Scientists from Uppsala University and the European Synchrotron Radiation Facility used X-ray synchrotron microtomography to study the fossilised interior of the skeleton's humerus, finding organised tubular structures akin to modern vertebrate bone marrow.[31] Eusthenopteron is closely related to the early tetrapods, which ultimately evolved into the land-dwelling mammals and lizards of the present day.[31]

See also

References

  1. ^ Schmidt, Richard F.; Lang, Florian; Heckmann, Manfred (2010-11-30). "What are the organs of the immune system?". © IQWiG (Institute for Quality and Efficiency in Health Care): 3/7.
  2. ^ C., Farhi, Diane (2009). Pathology of bone marrow and blood cells (2nd ed.). Philadelphia: Wolters Kluwer Health/Lippincott William & Wilkins. ISBN 9780781770934. OCLC 191807944.
  3. ^ Arikan, Hüseyin; Çiçek, Kerim (2014). "Haematology of amphibians and reptiles: a review" (PDF). North-Western Journal of Zoology. 10: 190–209.
  4. ^ Katherine, Abel (2013). Official CPC Certification Study Guide. American Medical Association.
  5. ^ Vunjak-Novakovic, G.; Tandon, N.; Godier, A.; Maidhof, R.; Marsano, A.; Martens, T. P.; Radisic, M. (2010). "Challenges in Cardiac Tissue Engineering". Tissue Engineering Part B: Reviews. 16 (2): 169–187. doi:10.1089/ten.teb.2009.0352. PMC 2946883. PMID 19698068.
  6. ^ a b c Birbrair, Alexander; Frenette, Paul S. (2016-03-01). "Niche heterogeneity in the bone marrow". Annals of the New York Academy of Sciences. 1370 (1): 82–96. doi:10.1111/nyas.13016. ISSN 1749-6632. PMC 4938003. PMID 27015419.
  7. ^ a b "Antibody Transforms Stem Cells Directly Into Brain Cells". Science Daily. 22 April 2013. Retrieved 24 April 2013.
  8. ^ a b "Research Supports Promise of Cell Therapy for Bowel Disease". Wake Forest Baptist Medical Center. 28 February 2013. Retrieved 5 March 2013.
  9. ^ a b Chan, Brian Y.; Gill, Kara G.; Rebsamen, Susan L.; Nguyen, Jie C. (2016-10-01). "MR Imaging of Pediatric Bone Marrow". RadioGraphics. 36 (6): 1911–1930. doi:10.1148/rg.2016160056. ISSN 0271-5333. PMID 27726743.
  10. ^ Poulton, T B; Murphy, W D; Duerk, J L; Chapek, C C; Feiglin, D H (1993-12-01). "Bone marrow reconversion in adults who are smokers: MR Imaging findings". American Journal of Roentgenology. 161 (6): 1217–1221. doi:10.2214/ajr.161.6.8249729. ISSN 0361-803X. PMID 8249729.
  11. ^ a b c d Raphael Rubin & David S. Strayer (2007). Rubin's Pathology: Clinicopathologic Foundations of Medicine. Lippincott Williams & Wilkins. p. 90. ISBN 978-0-7817-9516-6.
  12. ^ Appendix A:IV in Wintrobe's clinical hematology (9th edition). Philadelphia: Lea & Febiger (1993).
  13. ^ "The Red Cell Membrane: structure and pathologies" (PDF). Australian Centre for Blood Diseases/Monash University. Retrieved 24 January 2015.
  14. ^ The Lymphatic System. Allonhealth.com. Retrieved 5 December 2011.
  15. ^ Bonnet, D; Dick, JE (1997). "Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell". Nature Medicine. 3 (7): 730–737. doi:10.1038/nm0797-730. PMID 9212098.
  16. ^ a b "Bone Marrow Aspiration and Biopsy". Lab Tests Online UK. Retrieved 16 February 2013.
  17. ^ Mahla RS (2016). "Stem cells application in regenerative medicine and disease threpeutics". International Journal of Cell Biology. 2016 (7): 1–24. doi:10.1155/2016/6940283. PMC 4969512. PMID 27516776.CS1 maint: Uses authors parameter (link)
  18. ^ Ellmann, Stephan; Beck, Michael; Kuwert, Torsten; Uder, Michael; Bäuerle, Tobias (2015). "Multimodal imaging of bone metastases: From preclinical to clinical applications". Journal of Orthopaedic Translation. 3 (4): 166–177. doi:10.1016/j.jot.2015.07.004. PMC 5986987. PMID 30035055.
  19. ^ Nishida, Y; Matsue, Y; Suehara, Y; Fukumoto, K; Fujisawa, M; Takeuchi, M; Ouchi, E; Matsue, K (August 2015). "Clinical and prognostic significance of bone marrow abnormalities in the appendicular skeleton detected by low-doe whole-body multidetector computed tomography in patients with multiple myeloma". Blood Cancer Journal. 5 (7): e329. doi:10.1038/bcj.2015.57. ISSN 2044-5385. PMID 26230953.
  20. ^ Poulton, TB; Murphy, WD; Duerk, JL; Chapek, CC; Feiglin, DH (December 1993). "Bone marrow reconversion in adults who are smokers: MR Imaging findings". AJR. American Journal of Roentgenology. 161 (6): 1217–21. doi:10.2214/ajr.161.6.8249729. PMID 8249729.
  21. ^ Shah, LM; Hanrahan, CJ (December 2011). "MRI of spinal bone marrow: part I, techniques and normal age-related appearances". AJR. American Journal of Roentgenology. 197 (6): 1298–308. doi:10.2214/ajr.11.7005. PMID 22109283.
  22. ^ Vande Berg, BC; Lecouvet, FE; Galant, C; Maldague, BE; Malghem, J (July 2005). "Normal variants and frequent marrow alterations that simulate bone marrow lesions at MR imaging". Radiologic Clinics of North America. 43 (4): 761–70, ix. doi:10.1016/j.rcl.2005.01.007. PMID 15893536.
  23. ^ "Definition: 'M:E Ratio'". Stedman's Medical Dictionary via MediLexicon.com. 2006. Retrieved 20 December 2012.
  24. ^ "Bone marrow transplantation". UpToDate.com. Retrieved 12 April 2014.
  25. ^ "Bone marrow 'frees men of HIV drugs'". BBC. 3 July 2013. Retrieved 3 July 2013.
  26. ^ "Stem-Cell Transplants Erase HIV In Two Men". PopSci. 3 July 2013. Retrieved 3 July 2013.
  27. ^ "HIV Returns in Two Men Thought 'Cured' by Bone Marrow Transplants". RH Reality Check. 10 December 2013. Retrieved 10 December 2013.
  28. ^ National Marrow Donor Program Donor Guide Archived 8 September 2008 at the Wayback Machine. Marrow.org. Retrieved 5 November 2012.
  29. ^ Bone marrow donation: What to expect when you donate. Mayo Clinic. Retrieved 16 February 2013.
  30. ^ McGuckin, C. P.; Forraz, N.; Baradez, M. -O.; Navran, S.; Zhao, J.; Urban, R.; Tilton, R.; Denner, L. (2005). "Production of stem cells with embryonic characteristics from human umbilical cord blood". Cell Proliferation. 38 (4): 245–255. doi:10.1111/j.1365-2184.2005.00346.x. PMID 16098183.
  31. ^ a b c Sanchez, S.; Tafforeau, P.; Ahlberg, P. E. (2014). "The humerus of Eusthenopteron: a puzzling organization presaging the establishment of tetrapod limb bone marrow". Proceedings of the Royal Society B: Biological Sciences. 281 (1782): 20140299. doi:10.1098/rspb.2014.0299. PMC 3973280. PMID 24648231.

External links

Further reading

Allotransplantation

Allotransplant (allo- meaning "other" in Greek) is the transplantation of cells, tissues, or organs to a recipient from a genetically non-identical donor of the same species. The transplant is called an allograft, allogeneic transplant, or homograft. Most human tissue and organ transplants are allografts.

It is contrasted with autotransplantation (from one part of the body to another in the same person), syngeneic transplantation (grafts transplanted between two genetically identical individuals of the same species) and xenotransplantation (from other species).

Allografts can be referred to as "homostatic" if they are biologically inert when transplanted, such as bone and cartilage.An immune response against an allograft or xenograft is termed rejection. An allogenic bone marrow transplant can result in an immune attack, called graft-versus-host disease.

Aplastic anemia

Aplastic anaemia is a rare disease in which the bone marrow and the hematopoietic stem cells that reside there are damaged. This causes a deficiency of all three blood cell types (pancytopenia): red blood cells (anemia), white blood cells (leukopenia), and platelets (thrombocytopenia). Aplastic refers to the inability of stem cells to generate mature blood cells.

It is more frequent in people in their teens and twenties, but is also common among the elderly. It can be caused by heredity, immune disease, or exposure to chemicals, drugs, or radiation. However, in about half the cases, the cause is unknown.The definitive diagnosis is by bone marrow biopsy; normal bone marrow has 30–70% blood stem cells, but in aplastic anaemia, these cells are mostly gone and replaced by fat.First line treatment for aplastic anaemia consists of immunosuppressive drugs, typically either anti-lymphocyte globulin or anti-thymocyte globulin, combined with corticosteroids and ciclosporin. Hematopoietic stem cell transplantation is also used, especially for patients under 30 years of age with a related matched marrow donor.The disease is also known as the cause of death of Eleanor Roosevelt and Marie Curie.

BST1

ADP-ribosyl cyclase 2 is an enzyme that in humans is encoded by the BST1 gene.Bone marrow stromal cell antigen-1 is a stromal cell line-derived glycosylphosphatidylinositol-anchored molecule that facilitates pre-B-cell growth. The deduced amino acid sequence exhibits 33% similarity with CD38. BST1 expression is enhanced in bone marrow stromal cell lines derived from patients with rheumatoid arthritis. The polyclonal B-cell abnormalities in rheumatoid arthritis may be, at least in part, attributed to BST1 overexpression in the stromal cell population.

Bone marrow examination

Bone marrow examination refers to the pathologic analysis of samples of bone marrow obtained by bone marrow biopsy (often called a trephine biopsy) and bone marrow aspiration. Bone marrow examination is used in the diagnosis of a number of conditions, including leukemia, multiple myeloma, lymphoma, anemia, and pancytopenia. The bone marrow produces the cellular elements of the blood, including platelets, red blood cells and white blood cells. While much information can be gleaned by testing the blood itself (drawn from a vein by phlebotomy), it is sometimes necessary to examine the source of the blood cells in the bone marrow to obtain more information on hematopoiesis; this is the role of bone marrow aspiration and biopsy.

Bone marrow suppression

Bone marrow suppression also known as myelotoxicity or myelosuppression, is the decrease in production of cells responsible for providing immunity (leukocytes), carrying oxygen (erythrocytes), and/or those responsible for normal blood clotting (thrombocytes). Bone marrow suppression is a serious side effect of chemotherapy and certain drugs affecting the immune system such as azathioprine. The risk is especially high in cytotoxic chemotherapy for leukemia.

Nonsteroidal anti-inflammatory drugs (NSAIDs), in some rare instances, may also cause bone marrow suppression. The decrease in blood cell counts does not occur right at the start of chemotherapy because the drugs do not destroy the cells already in the bloodstream (these are not dividing rapidly). Instead, the drugs affect new blood cells that are being made by the bone marrow. When myelosuppression is severe, it is called myeloablation.Many other drugs including common antibiotics may cause bone marrow suppression. Unlike chemotherapy the effects may not be due to direct destruction of stem cells but the results may be equally serious. The treatment may mirror that of chemotherapy-induced myelosuppression or may be to change to an alternate drug or to temporarily suspend treatment.

Because the bone marrow is the manufacturing center of blood cells, the suppression of bone marrow activity causes a deficiency of blood cells. This condition can rapidly lead to life-threatening infection, as the body cannot produce leukocytes in response to invading bacteria and viruses, as well as leading to anaemia due to a lack of red blood cells and spontaneous severe bleeding due to deficiency of platelets.

Parvovirus B19 inhibits erythropoiesis by lytically infecting RBC precursors in the bone marrow and is associated with a number of different diseases ranging from benign to severe. In immunocompromised patients, B19 infection may persist for months, leading to chronic anemia with B19 viremia due to chronic marrow suppression.

Bone tumor

A bone tumor is a neoplastic growth of tissue in bone. Abnormal growths found in the bone can be either benign (noncancerous) or malignant (cancerous).

Average five-year survival in the United States after being diagnosed with bone and joint cancer is 67%.

Erythropoiesis

Erythropoiesis (from Greek 'erythro' meaning "red" and 'poiesis' meaning "to make") is the process which produces red blood cells (erythrocytes). It is stimulated by decreased O2 in circulation, which is detected by the kidneys, which then secrete the hormone erythropoietin. This hormone stimulates proliferation and differentiation of red cell precursors, which activates increased erythropoiesis in the hemopoietic tissues, ultimately producing red blood cells (erythrocytes). In postnatal birds and mammals (including humans), this usually occurs within the red bone marrow. In the early fetus, erythropoiesis takes place in the mesodermal cells of the yolk sac. By the third or fourth month, erythropoiesis moves to the liver. After seven months, erythropoiesis occurs in the bone marrow. Increased level of physical activity can cause an increase in erythropoiesis. However, in humans with certain diseases and in some animals, erythropoiesis also occurs outside the bone marrow, within the spleen or liver. This is termed extramedullary erythropoiesis.

The bone marrow of essentially all the bones produces red blood cells until a person is around five years old. The tibia and femur cease to be important sites of hematopoiesis by about age 25; the vertebrae, sternum, pelvis and ribs, and cranial bones continue to produce red blood cells throughout life.

Fanconi anemia

Fanconi anaemia (FA) is a rare genetic disease resulting in impaired response to DNA damage. Although it is a very rare disorder, study of this and other bone marrow failure syndromes has improved scientific understanding of the mechanisms of normal bone marrow function and development of cancer. Among those affected, the majority develop cancer, most often acute myelogenous leukemia, and 90% develop bone marrow failure (the inability to produce blood cells) by age 40. About 60–75% of people have congenital defects, commonly short stature, abnormalities of the skin, arms, head, eyes, kidneys, and ears, and developmental disabilities. Around 75% of people have some form of endocrine problems, with varying degrees of severity.

FA is the result of a genetic defect in a cluster of proteins responsible for DNA repair via homologous recombination.Treatment with androgens and hematopoietic (blood cell) growth factors can help bone marrow failure temporarily, but the long-term treatment is bone marrow transplant if a donor is available. Because of the genetic defect in DNA repair, cells from people with FA are sensitive to drugs that treat cancer by DNA crosslinking, such as mitomycin C. The typical age of death was 30 years in 2000.FA occurs in about one per 130,000 births, with a higher frequency in Ashkenazi Jews in Israel and Afrikaners in South Africa. The disease is named after the Swiss pediatrician who originally described this disorder, Guido Fanconi. It should not be confused with Fanconi syndrome, a kidney disorder also named after Fanconi.

Hematology

Hematology, also spelled haematology, is the branch of medicine concerned with the study of the cause, prognosis, treatment, and prevention of diseases related to blood. It involves treating diseases that affect the production of blood and its components, such as blood cells, hemoglobin, blood proteins, bone marrow, platelets, blood vessels, spleen, and the mechanism of coagulation. Such diseases might include hemophilia, blood clots, other bleeding disorders and blood cancers such as leukemia, multiple myeloma, and lymphoma. The laboratory work that goes into the study of blood is frequently performed by a medical technologist or medical laboratory scientist. Many hematologists work as hematologist-oncologists, also providing medical treatment for all types of cancer. The term is from the Greek αἷμα, haima meaning "blood," and -λoγία meaning study.

Hematopoietic stem cell

Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This process is called haematopoiesis. This process occurs in the red bone marrow, in the core of most bones. In embryonic development, the red bone marrow is derived from the layer of the embryo called the mesoderm.

Hematopoiesis is the process by which all mature blood cells are produced. It must balance enormous production needs (the average person produces more than 500 billion blood cells every day) with the need to precisely regulate the number of each blood cell type in the circulation. In vertebrates, the vast majority of hematopoiesis occurs in the bone marrow and is derived from a limited number of hematopoietic stem cells (HSCs) that are multipotent and capable of extensive self-renewal.

HSCs give rise to both the myeloid and lymphoid lineages of blood cells. Myeloid and lymphoid lineages both are involved in dendritic cell formation. Myeloid cells include monocytes, macrophages, neutrophils, basophils, eosinophils, erythrocytes, and megakaryocytes to platelets. Lymphoid cells include T cells, B cells, and natural killer cells. The definition of hematopoietic stem cells has evolved since HSCs were first discovered in 1961. The hematopoietic tissue contains cells with long-term and short-term regeneration capacities and committed multipotent, oligopotent, and unipotent progenitors. HSCs constitute 1:10.000 of cells in myeloid tissue.

HSC transplants are used in the treatment of cancers and other immune system disorders.

Hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood. It may be autologous (the patient's own stem cells are used), allogeneic (the stem cells come from a donor) or syngeneic (from an identical twin).It is most often performed for patients with certain cancers of the blood or bone marrow, such as multiple myeloma or leukemia. In these cases, the recipient's immune system is usually destroyed with radiation or chemotherapy before the transplantation. Infection and graft-versus-host disease are major complications of allogeneic HSCT.Hematopoietic stem cell transplantation remains a dangerous procedure with many possible complications; it is reserved for patients with life-threatening diseases. As survival following the procedure has increased, its use has expanded beyond cancer to autoimmune diseases and hereditary skeletal dysplasias; notably malignant infantile osteopetrosis and mucopolysaccharidosis.

Leukemia

Leukemia, also spelled leukaemia, is a group of cancers that usually begin in the bone marrow and result in high numbers of abnormal white blood cells. These white blood cells are not fully developed and are called blasts or leukemia cells. Symptoms may include bleeding and bruising problems, feeling tired, fever, and an increased risk of infections. These symptoms occur due to a lack of normal blood cells. Diagnosis is typically made by blood tests or bone marrow biopsy.The exact cause of leukemia is unknown. A combination of genetic factors and environmental (non-inherited) factors are believed to play a role. Risk factors include smoking, ionizing radiation, some chemicals (such as benzene), prior chemotherapy, and Down syndrome. People with a family history of leukemia are also at higher risk. There are four main types of leukemia—acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML)—as well as a number of less common types. Leukemias and lymphomas both belong to a broader group of tumors that affect the blood, bone marrow, and lymphoid system, known as tumors of the hematopoietic and lymphoid tissues.Treatment may involve some combination of chemotherapy, radiation therapy, targeted therapy, and bone marrow transplant, in addition to supportive care and palliative care as needed. Certain types of leukemia may be managed with watchful waiting. The success of treatment depends on the type of leukemia and the age of the person. Outcomes have improved in the developed world. The average five-year survival rate is 57% in the United States. In children under 15, the five-year survival rate is greater than 60 to 85%, depending on the type of leukemia. In children with acute leukemia who are cancer-free after five years, the cancer is unlikely to return.In 2015, leukemia was present in 2.3 million people and caused 353,500 deaths. In 2012 it newly developed in 352,000 people. It is the most common type of cancer in children, with three quarters of leukemia cases in children being the acute lymphoblastic type. However, about 90% of all leukemias are diagnosed in adults, with AML and CLL being most common in adults. It occurs more commonly in the developed world.

Multiple myeloma

Multiple myeloma, also known as plasma cell myeloma, is a cancer of plasma cells, a type of white blood cell normally responsible for producing antibodies. Often, no symptoms are noticed initially. When advanced, bone pain, bleeding, frequent infections, and anemia may occur. Complications may include amyloidosis.The cause of multiple myeloma is unknown. Risk factors include obesity, radiation exposure, family history, and certain chemicals. The underlying mechanism involves abnormal plasma cells producing abnormal antibodies which can cause kidney problems and overly thick blood. The plasma cells can also form a mass in the bone marrow or soft tissue. When only one mass is present, it is known as a plasmacytoma, while more than one is known as multiple myeloma. Multiple myeloma is diagnosed based on blood or urine tests finding abnormal antibodies, bone marrow biopsy finding cancerous plasma cells, and medical imaging finding bone lesions. Another common finding is high blood calcium levels.Multiple myeloma is considered treatable, but generally incurable. Remissions may be brought about with steroids, chemotherapy, targeted therapy, and stem cell transplant. Bisphosphonates and radiation therapy are sometimes used to reduce pain from bone lesions.Globally, multiple myeloma affected 488,000 people and resulted in 101,100 deaths in 2015. In the United States, it develops in 6.5 per 100,000 people per year and 0.7% of people are affected at some point in their lives. It usually occurs around the age of 61 and is more common in men than women. It is uncommon before the age of 40. Without treatment, typical survival is seven months. With current treatments, survival is usually 4–5 years. This gives a five-year survival rate around 49%. The word myeloma is from the Greek myelo- meaning "marrow" and -oma meaning "tumor".

Myelodysplastic syndrome

Myelodysplastic syndromes (MDS) are a group of cancers in which immature blood cells in the bone marrow do not mature and therefore do not become healthy blood cells. Early on, there are typically no symptoms. Later symptoms may include feeling tired, shortness of breath, easy bleeding, or frequent infections. Some types may develop into acute myeloid leukemia.Risk factors include previous chemotherapy or radiation therapy, exposure to certain chemicals such as tobacco smoke, pesticides, and benzene, and exposure to heavy metals such as mercury or lead. Problems with blood cell formation result in some combination of low red blood cells, low platelets, and low white blood cells. Some types have an increase in immature blood cells, called blasts, in the bone marrow or blood. The types of MDS are based on specific changes in the blood cells and bone marrow.Treatments may include supportive care, drug therapy, and stem cell transplantation. Supportive care may include blood transfusions, medications to increase the making of red blood cells, and antibiotics. Drug therapy may include the medication lenalidomide, antithymocyte globulin, and azacitidine. Certain people can be cured with chemotherapy followed by a stem-cell transplant from a donor.About seven per 100,000 people are affected with about four per 100,000 people newly acquiring the condition each year. The typical age of onset is 70 years. The outlook depends on the type of cells affected, the number of blasts in the bone marrow or blood, and the changes present in the chromosomes of the affected cells. The typical survival time following diagnosis is 2.5 years. The conditions were first recognized in the early 1900s. The current name came into use in 1976.

Myelofibrosis

Primary myelofibrosis is a relatively rare bone marrow cancer. It is currently classified as a myeloproliferative neoplasm, in which the proliferation of an abnormal clone of hematopoietic stem cells in the bone marrow and other sites results in fibrosis, or the replacement of the marrow with scar tissue.The term myelofibrosis alone usually refers to primary myelofibrosis (PMF), also known as chronic idiopathic myelofibrosis (cIMF); the terms idiopathic and primary mean that in these cases the disease is of unknown or spontaneous origin. This is in contrast with myelofibrosis that develops secondary to polycythemia vera or essential thrombocythaemia. Myelofibrosis is a form of myeloid metaplasia, which refers to a change in cell type in the blood-forming tissue of the bone marrow, and often the two terms are used synonymously. The terms agnogenic myeloid metaplasia and myelofibrosis with myeloid metaplasia (MMM) were also used to refer to primary myelofibrosis.

Myeloid tissue

Myeloid tissue, in the bone marrow sense of the word myeloid (myelo- + -oid), is tissue of bone marrow, of bone marrow cell lineage, or resembling bone marrow, and myelogenous tissue (myelo- + -genous) is any tissue of, or arising from, bone marrow; in these senses the terms are usually used synonymously, as for example with chronic myeloid/myelogenous leukemia.

In hematopoiesis, myeloid or myelogenous cells are blood cells that arise from a progenitor cell for granulocytes, monocytes, erythrocytes, or platelets (the common myeloid progenitor, that is, CMP or CFU-GEMM), or in a narrower sense also often used, specifically from the lineage of the myeloblast (the myelocytes, monocytes, and their daughter types). Thus, although all blood cells, even lymphocytes, are normally born in the bone marrow in adults, myeloid cells in the narrowest sense of the term can be distinguished from lymphoid cells, that is, lymphocytes, which come from common lymphoid progenitor cells that give rise to B cells and T cells. Those cells' differentiation (that is, lymphopoiesis) is not complete until they migrate to lymphatic organs such as the spleen and thymus for programming by antigen challenge. Thus, among leukocytes, the term myeloid is associated with the innate immune system, in contrast to lymphoid, which is associated with the adaptive immune system. Similarly, myelogenous usually refers to nonlymphocytic white blood cells, and erythroid can often be used to distinguish "erythrocyte-related" from that sense of myeloid and from lymphoid.The word myelopoiesis has several senses in a way that parallels those of myeloid, and myelopoiesis in the narrower sense is the regulated formation specifically of myeloid leukocytes (myelocytes), allowing that sense of myelopoiesis to be contradistinguished from erythropoiesis and lymphopoiesis (even though all blood cells are normally produced in the marrow in adults).

Myeloid neoplasms always concern bone marrow cell lineage and are related to hematopoietic cells. Myeloid tissue can also be present in the liver and spleen in fetuses, and sometimes even in adults as well, which leads to extramedullary hematopoiesis.

There is one other sense of myeloid that means "pertaining to the spinal cord", but it is much less commonly used. Myeloid should not be confused with myelin, referring to an insulating layer covering the axons of many neurons.

National Marrow Donor Program

The National Marrow Donor Program (NMDP) is a nonprofit organization founded in 1986 and based in Minneapolis, Minnesota that operates the Be The Match Registry of volunteer hematopoietic cell donors and umbilical cord blood units in the United States.

The Be The Match Registry is the world's largest hematopoietic cell registry, listing nearly 16 million individuals and nearly 238,000 cord blood units. Hematopoietic cells from NMDP donors or cord blood units are used to transplant patients with a variety of blood, bone marrow or immune system disorders. As of September 2016, the NMDP had facilitated more than 80,000 transplants worldwide.

Osteoporotic bone marrow defect

Osteoporotic bone marrow defect is a condition which may be found in the body of the mandible. It is usually painless and found during routine radiographs. It appears as a poorly defined radiolucency (dark area) where there was a previous history of an extraction of a tooth. It may resemble a metastatic disease.

It is a localized increase of hematopoietic bone marrow that creates a radiolucent radiographic defect. They occur more commonly in women in the midyears and show a predilection for the molar region of the mandible. They are especially common in extraction sites. Scattered trabeculae may extend short distances into the defect or, in some instances, through it, giving the defect a fairly characteristic appearance. Naturally there are no clinical symptoms.

Tumors of the hematopoietic and lymphoid tissues

Tumors of the hematopoietic and lymphoid tissues (American English) or tumours of the haematopoietic and lymphoid malignancies (British English) are tumors that affect the blood, bone marrow, lymph, and lymphatic system. As those elements are all intimately connected through both the circulatory system and the immune system, a disease affecting one will often affect the others as well, making myeloproliferation and lymphoproliferation (and thus the leukemias and the lymphomas) closely related and often overlapping problems.

While uncommon in solid tumors, chromosomal translocations are a common cause of these diseases. This commonly leads to a different approach in diagnosis and treatment of haematological malignancies.

Haematological malignancies are malignant neoplasms ("cancer"), and they are generally treated by specialists in hematology and/or oncology. In some centers "haematology/oncology" is a single subspecialty of internal medicine while in others they are considered separate divisions (there are also surgical and radiation oncologists). Not all haematological disorders are malignant ("cancerous"); these other blood conditions may also be managed by a hematologist.

Hematological malignancies may derive from either of the two major blood cell lineages: myeloid and lymphoid cell lines. The myeloid cell line normally produces granulocytes, erythrocytes, thrombocytes, macrophages and mast cells; the lymphoid cell line produces B, T, NK and plasma cells. Lymphomas, lymphocytic leukemias, and myeloma are from the lymphoid line, while acute and chronic myelogenous leukemia, myelodysplastic syndromes and myeloproliferative diseases are myeloid in origin.

A subgroup of them are more severe and are known as haematological malignancies (British English)/hematological malignancies (American English) or blood cancer. They may also be referred to as liquid tumors.

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