Myelodysplastic syndromes (MDS), including myelodysplastic syndrome associated with isolated del(5q), or MDS del(5q), occur when a problem in the bone marrow prevents the production of normal blood cells so that immature or dysfunctional blood cells outnumber normal healthy blood cells. The several types of MDS differ in the types of abnormal blood cells produced. Though generally asymptomatic in early stages, patients in later stages of any form of MDS can suffer from extreme fatigue, paleness, shortness of breath, easy bruising and susceptibility to infection.
Definition
MDS del(5q) refers to the abnormal blood cell formation that results when cells lose a large stretch of DNA on the long “q” arm of chromosome 5. This mutation results in a very low number of red blood cells in the circulation and the appearance of a characteristic type of abnormal blood cell called hypolobulated micromegakaryocytes.
Symptoms
Patients with MDS del(5q) produce too few red blood cells and those they produce are abnormally large. Medically known as severe macrocytic anemia, this situation compromises oxygen delivery to the tissues, ultimately causing debilitating fatigue and weakness. Under a microscope, blood from a patient with MDS del(5q) shows hypolobulated micromegakaryocytes--the megakaryocytes, precursors of the platelet cells involved in blood clotting, are too small and lack the normal number of lobes. Loss of normal platelets causes easy bruising and bleeding and the appearance of pinpoint purple spots on the skin called petichiae.
Cause
According to Online Mendelian Inheritance in Man (OMIM), MDS del(5q) typically affects older people because the deletion mutation is not inherited, but occurs randomly in one bone marrow stem cell which then rapidly propagates itself, out-competing normal bone marrow stem cells. Although patients with MDS del(5q) lose a large stretch of DNA encoding many genes, OMIM identifies the loss of only one particular gene--the gene RPS14, encoding ribosomal protein S14--as the cause of MDS del(5q).
Effect
Ribosomes help assemble proteins. When cells lose one copy of the gene encoding RPS14, the ribosomes fail to process other proteins correctly--particularly those that ultimately drive blood cell production. As a result, the bone marrow makes the abnormal red blood cells and hypolobulated micromegakaryocytes.
Treatment
Although there is no cure for myelodysplastic syndrome, several therapies can reduce complications and prolong life. The Mayo Clinic reports that a drug called lenalidomide works especially well for people with MDS del(5q), reducing their need for blood transfusions. Erythropoietin, a growth factor that helps other forms of MDS, does not work well for patients with MDS del(5q).
As reviewed by Dr. Santata-Davila et al. in the March 2008 issue of the journal Leukemia Research, relative to patients with other forms of myelodysplastic syndrome, those with MDS del(5q) have a lower risk of progression to leukemia. They also survive longer.
References
- Mayo Clinic: Myelodysplastic syndromes
- Online Mendelian Inheritance in Man: Chromosome 5q deletion syndrome
- “Leukemia Research”; Chromosome 5q deletion: Specific diagnoses and cytogenetic details among 358 consecutive cases from a single institution; Rafael Santana-Davila et al.; March 2008.
