1. 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
- Author
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Mark J. Routbort, Guillermo Garcia-Manero, Kyle Devins, Paola Dal Cin, Kim Anh Do, Rashmi Kanagal-Shamanna, Olga Pozdnyakova, Sa A. Wang, Patricia T. Greipp, Robert P. Hasserjian, Tracy I. George, Kaaren K. Reichard, Keyur P. Patel, Eric D. Hsi, Adam Bagg, Attilio Orazi, L. Jeffrey Medeiros, Srdan Verstovsek, Heesun J. Rogers, Daniel A. Arber, Carlos E. Bueso-Ramos, Faezeh Darbaniyan, and Julia T. Geyer
- Subjects
Adult ,Pathology ,medicine.medical_specialty ,Myeloid ,Isochromosome ,Chronic myelomonocytic leukemia ,Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative ,Pathology and Forensic Medicine ,Bone Marrow ,hemic and lymphatic diseases ,medicine ,Humans ,Myeloproliferative neoplasm ,Retrospective Studies ,Biological Products ,Thrombocytosis ,business.industry ,food and beverages ,Myeloid leukemia ,medicine.disease ,Isochromosomes ,medicine.anatomical_structure ,Mutation ,Atypical chronic myeloid leukemia ,Bone marrow ,business - 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.
- Published
- 2022