A Novel Case of Myelodysplastic Syndrome With Isolated del(5q) and Concomitant CALR Mutation

Abstract

Myelodysplastic syndromes (MDSs) and myeloproliferative neoplasms (MPNs) are subgroups of myeloid neoplasms with chronic clinical courses. MDSs are characterized by simultaneous proliferation and apoptosis of hematopoietic cells and peripheral blood cytopenias. MDS with isolated del(5q) is a specific subtype of MDS that occurs primarily in older women, and is characterized by macrocytic anemia, increased platelet count, micromegakaryocytes, and favorable clinical course. MPNs are characterized by proliferation of hematopoietic cells, hypercellular marrows, and peripheral blood cytoses. Recently, calreticulin gene (CALR) mutations were described in a majority of MPN patients without ABL, JAK2, or MPL gene mutations. Patients with CALR mutations were preferentially male and had higher platelet counts and lower RBC and leukocyte counts than patients with JAK2 and MPL mutations. An 82-year-old woman with a platelet count of > 1,000 bil/L was diagnosed with essential thrombocythemia. Peripheral blood testing for JAK2 and MPL mutations was negative. She was treated with hydroxyurea and aspirin for two years, without significant response. A recent peripheral blood specimen was tested for CALR mutations and showed a 5-bp insertion in exon 9. A subsequent bone marrow biopsy showed normocellular marrow, mild megaloblastoid change of the granulocytic precursors, and a megakaryocytic hyperplasia with markedly increased numbers of hypo-and monolobate micromegakaryocytes. The peripheral smear showed a macrocytic anemia (hemoglobin [Hgb] 11.8 g/dL, mean corpuscular volume [MCV] 107.7 fL) and a marked thrombocytosis (platelets 769 bil/L). Chromosome analysis of bone marrow aspirate showed a del(5q). We are reporting a case of MDS with isolated del(5q) and concomitant CALR mutation. Although a small subset of patients with MDS with isolated del(5q) may have concomitant JAK2 mutations, to the best of our knowledge, this is the first reported case of MDS with isolated del(5q) and concomitant CALR mutation. Further data collection from such patients regarding their clinical behavior and response to therapy (eg, lenalidomide) is essential.