MYC overexpression is associated with an early disease progression from MDS to AML.
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Disease Progression
Female
Follow-Up Studies
Humans
Leukemia, Myeloid, Acute
/ drug therapy
Male
Middle Aged
Mutation
Myelodysplastic Syndromes
/ drug therapy
Neoplasms, Second Primary
/ drug therapy
Prognosis
Proto-Oncogene Proteins c-myc
/ genetics
Retrospective Studies
Survival Rate
Young Adult
AML
MDS
MYC
Journal
Leukemia research
ISSN: 1873-5835
Titre abrégé: Leuk Res
Pays: England
ID NLM: 7706787
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
received:
26
07
2021
revised:
09
10
2021
accepted:
19
10
2021
pubmed:
9
11
2021
medline:
13
1
2022
entrez:
8
11
2021
Statut:
ppublish
Résumé
Recent studies demonstrated that MYC epigenetically regulates AML cell survival and differentiation by suppressing IDH1/2-TET2-5hmC signaling and that MYC overexpression is associated with poor survival outcomes in multiple AML patient cohorts. However, the oncogenic roles of MYC in MDS remain to be explored. A total of 41 patients with de novo MDS were retrospectively identified using the Total Cancer Care database at the Moffitt Cancer Center. A total of 61 % of patients had low MYC expression and 39 % of patients had high MYC expression defined as MYC reactivity by immunohistochemical staining in ≥5% of bone marrow (BM) cells at the time of MDS diagnosis. The median MDS-to-AML progression free survival (PFS) was significantly shorter in the high MYC group (median PFS 9.3 vs. 17.7 months, HR = 2.328, p = 0.013). Further, overall survival (OS) was also shorter in the high MYC patients (median OS 19.7 vs. 51.7 months, HR = 2.299, p = 0.053). Multivariate analyses demonstrated that high MYC expression is an independent poor prognostic factor for the MDS-to-AML progression (HR = 2.275, p = 0.046). Our observations indicate that MYC may play a crucial role in MDS transformation to AML and the underlying mechanisms of MYC-driven MDS clonal expansion and leukemic transformation require further investigation.
Identifiants
pubmed: 34749168
pii: S0145-2126(21)01734-3
doi: 10.1016/j.leukres.2021.106733
pmc: PMC8643343
mid: NIHMS1750181
pii:
doi:
Substances chimiques
MYC protein, human
0
Proto-Oncogene Proteins c-myc
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
106733Subventions
Organisme : NCI NIH HHS
ID : K08 CA237627
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA076292
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.
Références
Leuk Res. 2019 Sep;84:106194
pubmed: 31357093
J Clin Oncol. 2014 Sep 1;32(25):2691-8
pubmed: 25092778
Cell Stem Cell. 2014 Oct 2;15(4):431-446
pubmed: 25280219
J Clin Oncol. 2021 May 10;39(14):1575-1583
pubmed: 33600210
Blood. 2012 Sep 20;120(12):2454-65
pubmed: 22740453
N Engl J Med. 2016 Jun 9;374(23):2209-2221
pubmed: 27276561
Blood. 2016 May 19;127(20):2391-405
pubmed: 27069254
Cell. 2010 Oct 15;143(2):313-24
pubmed: 20946988
Blood Cancer Discov. 2021 Mar;2(2):162-185
pubmed: 33860275
Nat Med. 2019 Jan;25(1):103-110
pubmed: 30510255
J Clin Oncol. 2021 May 10;39(14):1584-1594
pubmed: 33449813
Blood Adv. 2021 Feb 23;5(4):1017-1028
pubmed: 33591325
Cancer Cell. 2019 Nov 11;36(5):483-497.e15
pubmed: 31679823
Hematology Am Soc Hematol Educ Program. 2009;:385-95
pubmed: 20008224
Int J Lab Hematol. 2021 Feb;43(1):99-109
pubmed: 32812335
N Engl J Med. 2009 Nov 5;361(19):1872-85
pubmed: 19890130
Clin Lymphoma Myeloma Leuk. 2016 Nov;16(11):607-609
pubmed: 27693133
Leukemia. 2021 Apr;35(4):1145-1155
pubmed: 32728186
Semin Cancer Biol. 2006 Aug;16(4):253-64
pubmed: 16904903
Blood. 2006 Jul 15;108(2):419-25
pubmed: 16609072
Nat Med. 2018 Jan;24(1):103-112
pubmed: 29227476
Oncogene. 2002 Oct 17;21(47):7137-46
pubmed: 12370803
Blood. 2005 Oct 1;106(7):2452-61
pubmed: 15972450
Blood. 2017 Jan 26;129(4):424-447
pubmed: 27895058
Leuk Lymphoma. 2019 Jan;60(1):37-48
pubmed: 29741984
Mol Cell Biol. 2004 Apr;24(7):2890-904
pubmed: 15024077
Leukemia. 2016 Mar;30(3):666-73
pubmed: 26514544
Hematol Oncol. 2017 Sep;35(3):350-356
pubmed: 26856970
Oncotarget. 2016 Mar 22;7(12):14172-87
pubmed: 26871476
Blood. 1997 Mar 15;89(6):2079-88
pubmed: 9058730