Myeloproliferative Neoplasm Resembling Polycythemia Vera In a Patient with t(2;11)(p21;q23) Translocation and Persistently Elevated MiR-125b-1

Hematologic neoplasms associated with the chromosomal translocation t(2;11)(p21;q23) form a distinct genetic entity with diverse manifestations, and have been strongly linked with up-regulation of the microRNA miR-125b-1 (Bousquet et al, J Exp Med, 2008). Of 41 patients with myeloid malignancies and t(2;11)(p21;23) reported in the world's literature, all but 2 were cases of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), the latter cases frequently high-grade MDS transforming to AML. In 20 of 41 cases deletion of 5q was detected as a secondary cytogenetic abnormality. Only two cases of chronic myeloproliferative disorders associated with t(2;11)(p21;23) have been reported: one of chronic myeloid leukemia with a secondary t(9;22) (Ph) translocation (Royer-Pokora et al, Leukemia, 2003) and one of polycythemia vera (Acar et al, Amer J Hematol, 2006). We encountered a patient with a mixed myelodysplastic/myeloproliferative neoplasm clinically resembling polycythemia vera that was associated with t(2;11)(p21;q23) who was found to have persistent elevation in the blood of the microRNA miR-125b-1.

A 52 year-old male presented with upper extremity pain and headache. A CBC revealed the white blood cell count was 12.5 ×10³/uL (55% neutrophils, 12% lymphocytes, 8% monocytes, 5% eosinophils, 21% basophils), red blood cell count 6.62 × 10⁶/uL, hemoglobin 22.4 g/dL, hematocrit 68.1%, MCV 103 fL, and platelets 112 × 10³/uL. Bone marrow aspiration and biopsy revealed a markedly hypercellular marrow (100%) with 1+ reticulin fibrosis, mild trilineal dysplastic morphology, and a blast count of 0.8%. Cytogenetic studies disclosed 46, XY, t(2;11)(p21;q23) [4]/46, idem, del (5)(q15q31) [4]/46, XY, del (5) (q13q31) [2]/46, XY[10]. FISH studies were negative for BCR/ABL1 fusion and MLL rearrangement. Molecular analysis for the JAK2V617F allele was negative. A diagnosis of mixed myelodysplastic/myeloproliferative neoplasm, unclassified was made (WHO 2008). The patient was begun on hydroxyurea, 500 mg daily. Four months after diagnosis the blood counts were within normal range, at which time quantitative real-time PCR (qRT-PCR; Bousquet et al, J Exp Med, 2008) performed on a sample of whole blood revealed a twenty-fold elevation of the microRNA species miR-125b-1, compared to healthy donors (n=3), and JAK2V617F-negative (n=3) and JAK2V617F-positive (n=2) polycythemia vera controls. Repeat qRT-PCR performed on whole blood 15 months after diagnosis confirmed persistently elevated miR-125b-1, nearly 200-fold above healthy donor controls (n=3). 18 months after diagnosis the patient remains healthy, with normal blood counts on 500 mg of hydroxyurea daily (white blood cell count 5.54 ×10³/uL, red cell count 5.35 × 10⁶/uL, hemoglobin 13.7 g/dL, hematocrit 47.2%, MCV 88.2, platelets 132.0 × 10³/uL).

This case expands the clinical-pathologic spectrum of hematologic malignancies associated with t(2;11)(p21;23), and confirms the link between t(2;11)(p21;23) and up-regulation of miR-125b-1. Translocation t(2;11)(p21;23) with miR-125b-1 up-regulation should be considered as a rare possibility in the differential diagnosis of JAK2V617F-negative polycythemia vera.

No relevant conflicts of interest to declare.