Affiliation:
1. Department of Pathology and Laboratory Medicine University of Connecticut Farmington Connecticut USA
2. Department of Pathology and Laboratory Medicine, Weill Cornell Medical College Cornell University New York New York USA
3. Department of Pathology and Laboratory Medicine Hospital of the University of Pennsylvania Philadelphia Pennsylvania USA
4. Department of Pathology, Massachusetts General Hospital Harvard Medical School Boston Massachusetts USA
5. Department of Pathology University of Texas Southwestern Medical Center Dallas Texas USA
Abstract
AbstractIntroductionThe classic Philadelphia chromosome–negative myeloproliferative neoplasms (Ph (‐) MPNs), have variable potential for progression to the blast phase (MPN‐BP) of the disease. Except initiated by distinct driver mutations, MPN‐BP frequently carry similar genetic abnormalities defining acute myeloid leukemia myelodysplasia‐related (AML‐MR). Because of dissimilar initial pathogenesis, MPN‐BP and AML‐MR are retained under different disease categories. To determine if separately classifying these entities is justified, we compare MPN‐BP with AML‐MR patients based on mutational landscape and clinical parameters.Methods104 MPN‐BP patients and 145 AML‐MR patients were identified with available clinical, cytogenetic, and genetic data.ResultsAML‐MR patients presented with a higher blast count (median, 51% vs. 30%) while MPN‐BP patients had higher WBC counts, platelet counts and bone marrow cellularity (all p<0.0001). Patients with MPN‐BP showed similar genetic mutations with similar mutation pattern (functional domain, hotspot and locus involved by the mutations) but a different mutation rate from AML‐MR, with more frequent JAK2, CALR, MPL, ASXL1, IDH2, SETBP1 and SRSF2 mutations and less frequent TP53 and DNMT3A mutations. The overall survival (OS) of MPN‐BP (OS post‐BP‐progression) is comparable to that of AML‐MR (median OS, 9.5 months vs. 13.1 months, p=0.20). In addition, the subgroups of MPN‐BP show similar OS as AML‐MR. When harboring certain mutation such as TP53, ASXL1, DNMT3A, TET2, RUNX1, IDH1, IDH2, EZH2, U2AF1, BCOR and SRSF2, MPN‐BP and AML‐MR patients carrying the same somatic mutation show no difference in OS.ConclusionMPN‐BP and AML‐MR harbor similar somatic mutations and clinical outcomes, suggesting a unified clinical disease entity.