Myelodysplastic syndrome associated with acquired beta thalassemia: "BTMDS"

Abstract

Most patients with myelodysplastic syndromes (MDS) have macrocytic or normocytic anemia as a result of ineffective erythropoiesis due to clonal hematopoiesis. Occasional patients with MDS have microcytic red blood cell (RBC) indices in the absence of iron deficiency, however, and a high proportion of such patients have decreased alpha globin expression associated with somatic mutations in the chromatin remodeling factor ATRX; an established alternative mechanism for acquired alpha thalassemia in myeloid neoplasia is clonal deletion of the alpha globin cluster on chromosome 16p. This clinicopathological phenomenon has been called “acquired alpha thalassemia – myelodysplastic syndrome” (ATMDS). Here we describe a patient with new-onset microcytic anemia associated with acquired deletion of the beta globin cluster on chromosome 11, resulting in a beta thalassemia-MDS (BTMDS) phenotype. Phenotype-genotype correlation studies may reveal associations of specific mutation patterns with other recurrent MDS-associated hematological findings.

Figure 1. Diagnostic findings leading up to and following the diagnosis of BTMDS in the patient described

Approximately 2 years prior to diagnosis, this patient experienced a progressive decline in MCV and hemoglobin and an associated increase in RDW, suggesting acquired beta thalassemia was a result of an early clonal event in her MDS (A). The first date of transfusion is marked as the “outside presentation” (blue line, right graphs) and is associated with the nadir in hemoglobin. The date of intravenous iron administration (122 days prior to diagnosis) is indicated by a purple arrowhead. At diagnosis, her peripheral smear revealed anisopoikilocytosis and dysplastic neutrophils and rare circulating blasts (B; Wright-Giemsa, 400x). A supravital stain was performed (not shown) and did not reveal any HbH inclusions. Cytogenetic analysis revealed a complex karyotype (C); shown here is representative metaphase from the dominant clone. The white open arrows designate additional material on chromosome 5; loss of chromosome 6; a deletion at chromosome 7q21; a deletion at chromosome 12p11.2, loss of chromosome 14, an addition at chromosome 18q21, and an extra unidentified ring chromosome. Of these 15 metaphases, 2 had trisomy 8 (not shown). The red arrow identifies a derivative chromosome comprised of the long arm of chromosomes 11 and 17 [der(11;17)(q10;q10)], resulting in deletion of 11p and deletion of 17p. An additional 5 metaphases (not shown) were 43~45,XX,add(5)(q31),-6,add(7)(q21),-8,-9,+r. Abbreviations: MCV = mean cell volume; RDW = red cell distribution width; MDS = myelodysplastic syndromes.