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Clinicopathologic spectrum of myeloid neoplasms with concurrent myeloproliferative neoplasm driver mutations and SRSF2 mutations


Myeloproliferative neoplasms (MPNs) are frequently associated with classic driver mutations involving JAK2, MPL or CALR. SRSF2 is among the most frequently mutated splicing genes in myeloid neoplasms and SRSF2 mutations are known to confer a poor prognosis in patients with MPNs. In this study, we sought to evaluate the clinicopathologic spectrum of myeloid neoplasms harboring concurrent MPN-driver mutations and SRSF2 mutations. The study cohort included 27 patients, 22 (82%) men and five (19%) women, with a median age of 71 years (range, 51–84). These patients presented commonly with organomegaly (n = 15; 56%), monocytosis (n = 13; 48%), morphologic dysplasia (n = 11; 41%), megakaryocytic hyperplasia and/or clustering (n = 10; 37%) and bone marrow fibrosis >MF-1 (17/22; 77%). About one third of patients either initially presented with acute myeloid leukemia (AML) or eventually progressed to AML. Eighteen (68%) patients had a dominant clone with SRSF2 mutation and nine (33%) patients had a dominant clone with a classic MPN-associated driver mutation. Our data suggest that the presence of an SRSF2 mutation preceding the acquisition of a MPN driver mutations is not a disease-defining alteration nor is it restricted to any specific disease entity within the spectrum of myeloid neoplasms. In summary, patients with myeloid neoplasms associated with concurrent SRSF2 and classic MPN driver mutations have clinical and morphologic features close to that of classic MPNs often with frequent dysplasia and monocytosis.

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Fig. 1: Detailed spectrum of disease classification and molecular characterization of study group.
Fig. 2: Examples of spectrum of morphologic features in the study group.
Fig. 3: Mutational landscape in the study group, subclassified per disease group.
Fig. 4: Clonal dominance in relation to disease subclassification.
Fig. 5

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All data are available upon request.


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M.T. and S.L. designed the study, reviewed the pathology, collected and analyzed data. J.D.K., S.A.W., S.H., P.L. C.B.R., L.J.M. collected pathology data, M.J.R., R.L. K.P.P. C.Y.O., R.K.S. collected molecular data, SHE assisted in manuscript preparation, N.P., P.B. and S.V. manages patients and collected clinical data. All authors were involved in manuscript preparation and approved the final draft.

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Correspondence to Sanam Loghavi.

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The authors declare no competing interests.

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This study was approved by the Institutional Review Board (IRB) at MD Anderson Cancer Center (MDACC) and conducted in accord with the Declaration of Helsinki. Consent is not applicable for this retrospective study.

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Tashakori, M., Khoury, J.D., Routbort, M.J. et al. Clinicopathologic spectrum of myeloid neoplasms with concurrent myeloproliferative neoplasm driver mutations and SRSF2 mutations. Mod Pathol (2022).

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