Myelodysplastic syndrome with del (5q) and JAK2 V617F mutation transformed to acute myeloid leukaemia with complex karyotype

Dear Editor, Myelodysplastic syndrome with isolated del (5q) and JAK2 mutation is a distinct entity within the World Health Organization (WHO) category myelodysplastic syndromes (MDS) [1]. JAK2 is a gain of function mutation, typically associated with myeloproliferative neoplasms (MPN) [2]. However, approximately 5 % of patients with isolated del (5q) also harbours the JAK2 mutation [3, 4]. No correlation was found between isolated del (5q) JAK2 mutated cases and clinical presentation, morphological features, disease transformation or patient outcome [4, 5], although a few cases presented with higher platelet and WBC count [3]. Lenalidomide was reported to be an effective treatment for the disease [6]. We have recently studied a patient with del (5q) and JAK2 mutation transformed to acute myeloid leukaemia (AML) with complex karyotype and increased JAK2 mutation load. A 66-year-old female presented with moderate anaemia and high platelet count (haemoglobin 100 g/l, WBC 7.2 × 10/l, platelets 800 × 10/l). Neutrophils were 4.95×10/l, eosinophils 0.21×10/l, monocytes 0.14×10/l and lymphocytes 1.9×10/l. No blast cell was present in the peripheral blood. There was no splenoor hepatomegaly. On marrow aspirate, only eight metaphases showing a normal karyotype (46,XX) could be analysed, due to the lack of growth of an adequate number of metaphases and the poor cellularity of the sample. FISH analysis was limited to the study of 5q and demonstrated 5q31 deletion in 12 % of the nuclei. Thus, additional aberrations could not be identified. BCR/ABL rearrangements (p210, p190) were absent, while JAK2 mutation displayed an allele burden of 4.28 %. Bone marrow (BM) biopsy showed a 70 % cellularity, slight dyserythropoiesis, moderate myeloid hyperplasia and marked proliferation of the megakaryocytic lineage with some dysplasia. A few megakaryocytes were large with hyperlobulated nuclei; others were medium-sized, with round and/or hypolobulated nuclei. There were 3 % CD34-positive blasts and moderate reticulin fibrosis (WHOMF-2). (Fig. 1a– c, e). A strong nuclear p53 immunostaining was detected in 2 % haematopoietic cells (Fig. 1d). We proposed a diagnosis of MDS with del (5q) and JAK2 mutation. The patient did not receive any therapy. No organomegaly nor leukoerythroblastosis was reported during the course of the disease. Twenty-seven months later, she was admitted to the hospital because of persistent fever, severe anaemia and neutropenia (Hb level 7.5 g/l, WBC 2.3×10/l, neutrophils 0.75×10/l, platelets 137×10/l). There were 5 % blast cells in the peripheral blood. Chromosome banding analysis showed the following: 46, XX [1] / 45,XX, −7, del(5)(q13q33), del(13)(q14q34) [7] / 45, idem, del(2)(p12) [2]. FISH analysis demonstrated −7, del(5)(q31), del(13)(q14) (80 %) without BCR/ABL, AML1/ETO, PML/RARA, inv(16), MLL(11q23) translocation and +8. Molecular analysis did not identify FLT3 (ITD, D835), NPM1 (exon 12) or MLL-PTD mutations. Real-time quantitative polymerase chain reaction (RQ-PCR) detected 4164 WT1 copies/10 ABL copies and 55.6 % JAK2 mutation load. p53 sequencing analysis of exons 2–11 showed * Achille Pich achille.pich@unito.it