PMID- 32179032
OWN - NLM
STAT- MEDLINE
DCOM- 20210531
LR  - 20210602
IS  - 2152-2669 (Electronic)
IS  - 2152-2650 (Print)
IS  - 2152-2669 (Linking)
VI  - 20
IP  - 6
DP  - 2020 Jun
TI  - SF3B1 Mutations Negatively Predict for Response to Immunosuppressive Therapy in 
      Myelodysplastic Syndromes.
PG  - 400-406.e2
LID - S2152-2650(20)30008-2 [pii]
LID - 10.1016/j.clml.2019.12.023 [doi]
AB  - BACKGROUND: Immunosuppressive therapy (IST) yields durable hematologic 
      improvement (HI) in a subset of patients with lower-risk myelodysplastic syndrome 
      (MDS). Age, human leukocyte antigen (HLA)-DR15 positivity, and duration of 
      transfusion dependence are putative clinical variables predictive for response. 
      We investigated the effect of somatic gene mutations on response to IST in 
      lower-risk MDS. PATIENTS AND METHODS: Forty of 66 patients who received 
      antithymocyte globulin with or without cyclosporine A identified at the Moffitt 
      Cancer Center were molecularly profiled using a 49-gene myeloid panel. All 
      patients profiled received antithymocyte globulin, and cyclosporine A was 
      provided to 60% of patients. RESULTS: The overall frequency of HI was 42%. 
      Presence of a large granular lymphocytic clone, hypocellular bone marrow, 
      HLA-DR15 positivity, trisomy 8, and age had no influence on response to IST. 
      Among 40 patients evaluated by next-generation sequencing, the presence of an 
      SF3B1 mutation (MT) was significantly associated with IST nonresponse (1 of 9 
      SF3B1 MT, 11% vs. 21 of 31 wild type, 68%; P = .002). All patients with SF3B1 MT 
      had ring sideroblasts > 15% (RS) by morphology; the corresponding HI rate was 20% 
      among patients with RS versus 50% for those without RS (P = .09). CONCLUSION: 
      These findings support the clinical implementation of genomics in MDS. The 
      presence of an SF3B1 mutation adversely influences response to IST and should be 
      incorporated into treatment decisions upon validation of these findings.
CI  - Copyright (c) 2020. Published by Elsevier Inc.
FAU - Zhang, Qing
AU  - Zhang Q
AD  - Cancer Biology and Molecular Medicine, H. Lee Moffitt Cancer Center & Research 
      Institute, Tampa, FL.
FAU - Haider, Mintallah
AU  - Haider M
AD  - Malignant Hematology Department, H. Lee Moffitt Cancer Center & Research 
      Institute, Tampa, FL.
FAU - Al Ali, Najla H
AU  - Al Ali NH
AD  - Malignant Hematology Department, H. Lee Moffitt Cancer Center & Research 
      Institute, Tampa, FL.
FAU - Lancet, Jeffrey E
AU  - Lancet JE
AD  - Malignant Hematology Department, H. Lee Moffitt Cancer Center & Research 
      Institute, Tampa, FL.
FAU - Epling-Burnette, Pearlie K
AU  - Epling-Burnette PK
AD  - Immunology Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL.
FAU - List, Alan F
AU  - List AF
AD  - Malignant Hematology Department, H. Lee Moffitt Cancer Center & Research 
      Institute, Tampa, FL.
FAU - Padron, Eric
AU  - Padron E
AD  - Cancer Biology and Molecular Medicine, H. Lee Moffitt Cancer Center & Research 
      Institute, Tampa, FL; Malignant Hematology Department, H. Lee Moffitt Cancer 
      Center & Research Institute, Tampa, FL.
FAU - Komrokji, Rami S
AU  - Komrokji RS
AD  - Malignant Hematology Department, H. Lee Moffitt Cancer Center & Research 
      Institute, Tampa, FL. Electronic address: rami.komrokji@moffitt.org.
LA  - eng
GR  - P30 CA076292/CA/NCI NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
DEP - 20200110
PL  - United States
TA  - Clin Lymphoma Myeloma Leuk
JT  - Clinical lymphoma, myeloma & leukemia
JID - 101525386
RN  - 0 (Antilymphocyte Serum)
RN  - 0 (HLA-DR Serological Subtypes)
RN  - 0 (HLA-DR15 antigen)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Phosphoproteins)
RN  - 0 (RNA Splicing Factors)
RN  - 0 (SF3B1 protein, human)
RN  - 83HN0GTJ6D (Cyclosporine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antilymphocyte Serum/*administration & dosage
MH  - Cyclosporine/*administration & dosage
MH  - Female
MH  - HLA-DR Serological Subtypes/genetics/metabolism
MH  - Humans
MH  - Immunosuppressive Agents/*administration & dosage
MH  - Male
MH  - Middle Aged
MH  - *Mutation
MH  - *Myelodysplastic Syndromes/drug therapy/genetics/metabolism/mortality
MH  - Phosphoproteins/*genetics/metabolism
MH  - Predictive Value of Tests
MH  - RNA Splicing Factors/*genetics/metabolism
PMC - PMC7771378
MID - NIHMS1653202
OTO - NOTNLM
OT  - Antithymocyte globulin
OT  - Hematologic improvement
OT  - MDS
OT  - Response biomarkers
OT  - Somatic mutations
COIS- Disclosure The authors have stated that they have no conflict of interest.
EDAT- 2020/03/18 06:00
MHDA- 2021/06/01 06:00
PMCR- 2021/06/01
CRDT- 2020/03/18 06:00
PHST- 2019/09/16 00:00 [received]
PHST- 2019/12/23 00:00 [revised]
PHST- 2019/12/28 00:00 [accepted]
PHST- 2020/03/18 06:00 [pubmed]
PHST- 2021/06/01 06:00 [medline]
PHST- 2020/03/18 06:00 [entrez]
PHST- 2021/06/01 00:00 [pmc-release]
AID - S2152-2650(20)30008-2 [pii]
AID - 10.1016/j.clml.2019.12.023 [doi]
PST - ppublish
SO  - Clin Lymphoma Myeloma Leuk. 2020 Jun;20(6):400-406.e2. doi: 
      10.1016/j.clml.2019.12.023. Epub 2020 Jan 10.