Concurrent Mutations in SF3B1 and PHF6 in Myeloid Neoplasms

Authors

Zhuang Zuo
L Jeffrey Medeiros
Sofia Garces
Mark J Routbort
Chi Young Ok
Sanam Loghavi
Rashmi Kanagal-Shamanna
Fatima Zahra Jelloul
Guillermo Garcia-Manero
Kelly S Chien
Keyur P Patel
Rajyalakshmi Luthra
C Cameron Yin

Publication Date

12-21-2022

Journal

Biology

DOI

10.3390/biology12010013

PMID

36671709

PMCID

PMC9855138

PubMedCentral® Posted Date

12-21-2022

PubMedCentral® Full Text Version

Post-print

Abstract

It has been reported that gene mutations in SF3B1 and PHF6 are mutually exclusive. However, this observation has never been rigorously assessed. We report the clinicopathologic and molecular genetic features of 21 cases of myeloid neoplasms with double mutations in SF3B1 and PHF6, including 9 (43%) with myelodysplastic syndrome, 5 (24%) with acute myeloid leukemia, 4 (19%) with myeloproliferative neoplasms, and 3 (14%) with myelodysplastic/myeloproliferative neoplasms. Multilineage dysplasia with ring sideroblasts, increased blasts, and myelofibrosis are common morphologic findings. All cases but one had diploid or non-complex karyotypes. SF3B1 mutations were detected in the first analysis of all the patients. PHF6 mutations occurred either concurrently with SF3B1 mutations or in subsequent follow-up samples and are associated with disease progression and impending death in most cases. Most cases had co-mutations, the most common being ASXL1, RUNX1, TET2, and NRAS. With a median follow-up of 39 months (range, 3-155), 17 (81%) patients died, 3 were in complete remission, and 1 had persistent myelodysplastic syndrome. The median overall survival was 51 months. In summary, concurrent mutations in SF3B1 and PHF6 are rare, but they do exist in a variety of myeloid neoplasms, with roles as early initiating events and in disease progression, respectively.

Keywords

PHF6, SF3B1, myeloid neoplasms

Published Open-Access

yes

Recommended Citation

Zuo, Zhuang; Medeiros, L Jeffrey; Garces, Sofia; et al., "Concurrent Mutations in SF3B1 and PHF6 in Myeloid Neoplasms" (2022). Faculty, Staff and Student Publications. 3368.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/3368