Chromosome 5q deletion syndrome

Presentation

The 5q-syndrome is characterized by macrocytic anemia, often a moderate thrombocytosis, erythroblastopenia, megakaryocyte hyperplasia with nuclear hypolobation, and an isolated interstitial deletion of chromosome 5. The 5q- syndrome is found predominantly in females of advanced age.

Causes

Several genes in the deleted region appear to play a role in the pathogenesis of 5q-syndrome. Haploinsufficiency of RPS14 plays a central role, and contributes to the anemia via both p53-dependent and p53-independent tumor suppressor effects. Other genes at this region include miR-145 and miR-146a, whose deletion is associated with the megakaryocytic dysplasia and thrombocytosis seen in 5q- syndrome; SPARC, which has antiproliferative and antiangiogenic effects; and the candidate tumor suppressors EGR1, CTNNA1, and CDC25C.

Histology

This syndrome affects bone marrow cells causing treatment-resistant anemia and myelodysplastic syndromes that may lead to acute myelogenous leukemia. Examination of the bone marrow shows characteristic changes in the megakaryocytes. They are more numerous than usual, small and mononuclear. There may be accompanying erythroid hypoplasia in the bone marrow.

Treatment

Lenalidomide has activity in 5q- syndrome and is FDA approved for red blood cell (RBC) transfusion-dependent anemia due to low or intermediate-1 (int-1) risk myelodysplastic syndrome (MDS) associated with chromosome 5q deletion with or without additional cytogenetic abnormalities. There are several possible mechanisms that link the haploinsufficiency molecular lesions with lenalidomide sensitivity.

References

References

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3. {{OMIM. 153550. 5q- syndrome
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7. (2014). "Ribosomopathies: Mechanisms of disease". Clinical Medicine Insights: Blood Disorders.
8. Starczynowski DT. (January 2010). "Identification of miR-145 and miR-146a as mediators of the 5q- syndrome phenotype". Nature Medicine.
9. (2012). "A critical review of the molecular pathophysiology of lenalidomide sensitivity in 5q – myelodysplastic syndromes". Leukemia & Lymphoma.