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Krista Wed Nov 7, 2007 01:11 PM

Question for Student Paper
I'm writing a paper, and had a question regarding how bone marrow failure is caused. I have read in an AA&MDS pamphlet written by Dr. Neal S. Young that the body attacks the blood cells/stem cells, causing their low counts in the bloodstream. But I have also read that it is because damage has ocurred to the stem cells, due to genetics or enviornment, or unknown. Does it depend on the particular disease, or is it something we are just unsure of? Thanks for your help, it could really help my paper.

"Pathophysiology: Bone marrow failure can be inherited or acquired. It can involve just 1 cell line or all 3 cell lines. The pathophysiology of these defects includes the following mechanisms of action: (1) a decrease in or damage to the hematopoietic stem cells and their microenvironment, resulting in hypoplastic or aplastic bone marrow; (2) maturation defects, eg, vitamin B-12 or folate deficiency; and (3) differentiation defects, eg, myelodysplasia."

Neil Cuadra Wed Nov 7, 2007 04:03 PM

Bone marrow failure encompasses a number of diseases. This website is focused on three related bone marrow failure diseases: aplastic anemia (AA), myelodysplastic syndromes (MDS), and paroxysmal nocturnal hemoglobinuria (PNH). MDS itself is a family of diseases.

I collected some facts about AA, MDS, and PNH for you:
Aplastic anemia is acquired 80% of the time. Although it is considered an autoimmune condition, the original cause or trigger is usually unknown. Possible causes include certain chemicals (especially benzene), hepatitis and other viruses, radiation, and certain drugs. Even pregnancy has been associated with aplastic anemia.

The 20% of AA patients for whom AA is congenital (inherited) often have another diagnosis, such as Fanconi anemia, with AA not the primary diagnosis.

About two thirds of myelodysplastic syndromes (MDS) cases are idiopathic (original cause unknown). Benzene, other chemicals, and viruses may be causes, but specific exposures are usually hard to pinpoint. When a cause for MDS is known, it's often because MDS is secondary, a result of previous chemotherapy or radiation.

Paroxysmal nocturnal hemoglobinuria (PNH) is a specific genetic defect that is acquired, not inherited. It's unknown whether there is a genetic predisposition for PNH.

AA and PNH overlap; many patients have both. About 20% of AA patients also have PNH at time of first diagnosis, and immunosuppressive therapy for AA can result in PNH. Identifying risk factors for PNH, other than prior AA, is a subject of research.
See also the information and links on our Bone Marrow Failure Diseases page.

Krista Sun Nov 11, 2007 07:46 PM

I appreciate your reply, but I'm not sure I was very clear on the question. What I meant was, what is the result of the general diagnosis? Is it that damage had originally ocurred to the bone marrow cells, or to the stem cells, or to the blood cells, or to the body's ability to identify foreign cells in the body? Is it all three? What cells started the chain reaction? I've been getting diffrent answers. Some just say that cells are damaged. Which cells are damaged? I don't want to misword something so that it is inaccurate. I hope this helps. Thanks!

Birgitta-A Mon Nov 12, 2007 06:25 AM

The cause of MDS
Hi Krista,
There is no answer to your questions yet. You ask if the damage has occured to the bone marrow cells, to the stem cells, the blood cells or to the body´s ability to identify foreign cells in the body.

If the stem cells in the bone marrow are damaged the blood cells will be damaged since they develope from stem cells.

You can see in this abstract from PubMed what some researchers have written lately about the cause of MDS:

"Molecular Targets in Myelodysplastic Syndromes
Hofmann WK, Nolte F.
Department of Hematology and Oncology, University Hospital Benjamin Franklin, Charité, Hindenburgdamm 30, 12203 Berlin, Germany.
Cancer Treat Rev. 2007 Sep 27

Myelodysplastic syndromes are characterized by peripheral cytopenias (few cells) in combination with a hyperplastic (tending to excess of formative action) bone marrow.

The classification according to the WHO includes mainly morphological criteria (the form of the blood cells like abnormal granules in cells, abnormal nuclear shape and size) and is supplemented by the International Prognostic Scoring System which takes cytogenetical changes (development and variation of cells like damage to the chromosomes or DNA of bone marrow cells) into consideration when determining the prognosis of MDS.

The underlying mechanisms causing primary MDS requires further work. Different molecular alterations which have been described, suggest that it is a multistep alteration to the haematopoietic stem cells that include genes involved in cell cycle control, mitotic checkpoints as well as growth factor receptors.

Secondary signal proteins and transcription factors which gives the cell a growth advantage over its normal counterpart, may be affected as well. The accumulation of such defects may finally cause the leukaemic transformation of MDS."
Kind regards

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