Myelodysplastic/Myeloproliferative Neoplasms-Unclassifiable With Isolated Isochromosome 17q Represents a Distinct Clinico-Biologic Subset: A Multi-Institutional Collaborative Study From the Bone Marrow Pathology Group

Authors

Rashmi Kanagal-Shamanna
Attilio Orazi
Robert P Hasserjian
Daniel A Arber
Kaaren Reichard
Eric D Hsi
Adam Bagg
Heesun Joyce Rogers
Julia Geyer
Faezeh Darbaniyan
Kim-Anh Do
Kyle M Devins
Olga Pozdnyakova
Tracy I George
Paola Dal Cin
Patricia T Greipp
Mark J Routbort
Keyur Patel
Guillermo Garcia-Manero
Srdan Verstovsek
L Jeffrey Medeiros
Sa A Wang
Carlos Bueso-Ramos

Publication Date

4-1-2022

Journal

Modern Pathology

Abstract

Classification of myeloid neoplasms with isolated isochromosome i(17q) [17p deletion with inherent monoallelic TP53 loss plus 17q duplication] is controversial. Most cases fall within the WHO unclassifiable myelodysplastic/myeloproliferative neoplasms (MDS/MPN-U) category. The uniformly dismal outcomes warrant better understanding of this entity. We undertook a multi-institutional retrospective study of 92 adult MDS/MPN-U cases from eight institutions. Twenty-nine (32%) patients had isolated i(17q) [MDS/MPN-i(17q)]. Compared to MDS/MPN without i(17q), MDS/MPN-i(17q) patients were significantly younger, had lower platelet and absolute neutrophil counts, and higher frequency of splenomegaly and circulating blasts. MDS/MPN-i(17q) cases showed frequent bilobed neutrophils (75% vs. 23%; P = 0.03), hypolobated megakaryocytes (62% vs. 20%; P = 0.06), and a higher frequency of SETBP1 (69% vs. 5%; P = 0.002) and SRSF2 (63% vs. 5%; P = 0.006) mutations that were frequently co-existent (44% vs. 0%; P = 0.01). TP53 mutations were rare. The mutation profile of MDS/MPN-U-i(17q) was similar to other myeloid neoplasms with i(17q) including atypical chronic myeloid leukemia, chronic myelomonocytic leukemia, myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis, myelodysplastic syndrome and acute myeloid leukemia, with frequent concomitant SETBP1/SRSF2 mutations observed across all the diagnostic entities. Over a median follow-up of 52 months, patients with MDS/MPN-i(17q) showed a shorter median overall survival (11 vs. 28 months; P < 0.001). The presence of i(17q) retained independent poor prognostic value in multivariable Cox-regression analysis [HR 3.686 (1.17-11.6); P = 0.026] along with splenomegaly. We suggest that MDS/MPN-i(17q) warrants recognition as a distinct subtype within the MDS/MPN-U category based on its unique clinico-biologic features and uniformly poor prognosis.

Keywords

Adult, Biological Products, Bone Marrow, Humans, Isochromosomes, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative, Mutation, Retrospective Studies

Comments

This article has been corrected. See Mod Pathol. 2021 Dec 13.

DOI

10.1038/s41379-021-00961-0

PMID

34775472

PMCID

PMC8967812

PubMedCentral® Posted Date

5-13-2022

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes