TY - JOUR
T1 - Concurrent Mutations in SF3B1 and PHF6 in Myeloid Neoplasms
AU - Zuo, Zhuang
AU - Medeiros, L. Jeffrey
AU - Garces, Sofia
AU - Routbort, Mark J.
AU - Ok, Chi Young
AU - Loghavi, Sanam
AU - Kanagal-Shamanna, Rashmi
AU - Jelloul, Fatima Zahra
AU - Garcia-Manero, Guillermo
AU - Chien, Kelly S.
AU - Patel, Keyur P.
AU - Luthra, Rajyalakshmi
AU - Yin, C. Cameron
N1 - Publisher Copyright:
© 2022 by the authors.
PY - 2023/1
Y1 - 2023/1
N2 - 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.
AB - 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.
KW - myeloid neoplasms
KW - PHF6
KW - SF3B1
UR - http://www.scopus.com/inward/record.url?scp=85146794278&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85146794278&partnerID=8YFLogxK
U2 - 10.3390/biology12010013
DO - 10.3390/biology12010013
M3 - Article
C2 - 36671709
AN - SCOPUS:85146794278
SN - 2079-7737
VL - 12
JO - Biology
JF - Biology
IS - 1
M1 - 13
ER -