The implication of identifying JAK2(V617F) in myeloproliferative neoplasms and myelodysplastic syndromes with bone marrow fibrosis

The myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS) occasionally demonstrate overlapping morphological features including hypercellularity, mild/nonspecific dysplastic changes and variable bone marrow fibrosis. Thus, when the associated bone marrow fibrosis results in a suboptimal specimen for morphological evaluation, the descriptive diagnosis “fibrotic marrow with features indeterminate for MDS versus MPN” is often applied. The JAK2(V617F) mutation was recently shown to be frequently identified in MPN, but it is rarely present in other myeloid disorders. However, the diagnostic utility of JAK2(V617F) screening in hypercellular bone marrow specimens with fibrosis has not been previously investigated. Using a real-time polymerase chain reaction melting-curve assay capable of detecting JAK2(V617F) in archived fixed materials, we retrospectively studied JAK2(V617F) in 45 cases with fibrotic hypercellular bone marrow at initial presentation, including 19 cases initially described as “with features indeterminate for MDS versus MPN”. These 19 cases were reclassified into more specific categories of MDS (n = 14) or MPN (n = 5) based on the availability of subsequent clinical data and/or bone marrow examinations. The JAK2(V617F) allele was identified in 17 out of 18 BCR/ABL gene-negative MPN cases with marrow fibrosis, whereas only wild-type alleles were identified in the remaining non-MPN cases. Importantly, JAK2(V617F) alleles were seen in all five cases of “with features indeterminate for MDS versus MPN” at initial presentation that were later determined to be MPN, but they were absent in the 14 cases later determined to be MDS. Our results suggest that JAK2(V617F) allele evaluation can be a useful ancillary test for discriminating MDS from MPN in specimens with bone marrow fibrosis.