Comparison of myeloid neoplasms with nonclassic 3q26.2/MECOM versus classic inv(3)/t(3;3) rearrangements reveals diverse clinicopathologic features, genetic profiles, and molecular mechanisms of MECOM activation.
MECOM
genomic profile
molecular mechanism
myeloid neoplasm
Journal
Genes, chromosomes & cancer
ISSN: 1098-2264
Titre abrégé: Genes Chromosomes Cancer
Pays: United States
ID NLM: 9007329
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
revised:
09
10
2021
received:
08
06
2021
accepted:
12
10
2021
pubmed:
21
10
2021
medline:
18
3
2022
entrez:
20
10
2021
Statut:
ppublish
Résumé
MECOM rearrangements are recurrent in myeloid neoplasms and associated with poor prognosis. However, only inv(3)(q21q26.2) and t(3;3)(q21;q26.2), the classic MECOM rearrangements resulting in RPN1-MECOM rearrangement with Mecom overexpression and GATA2 haploinsufficiency, define the distinct subtype of acute myeloid leukemia (AML), and serve as presumptive evidence for myelodysplastic syndrome based on the current World Health Organization classification. Myeloid neoplasms with nonclassic 3q26.2/MECOM rearrangements have been found to be clinically aggressive, but comparative analysis of clinicopathologic and genomic features is limited. We retrospectively studied cohorts of myeloid neoplasms with classic and nonclassic MECOM rearrangements. Cases with classic rearrangements consisted predominantly of AML, often with inv(3) or t(3;3) as the sole chromosome abnormality, whereas the group of nonclassic rearrangements included a variety of myeloid neoplasms, often with complex karyotype without TP53 mutations and similarly dismal overall survival. Immunohistochemistry revealed Mecom protein overexpression in both groups, but overexpression in cases with nonclassic rearrangements was mediated through a mechanism other than GATA2 distal enhancer involvement typical for classic rearrangement. Our results demonstrated that myeloid neoplasms with nonclassic 3q26.2/MECOM rearrangements encompass a diverse group of diseases with poor clinical outcome, overexpression of Mecom protein as a result of the nonclassic mechanism of MECOM activation.
Substances chimiques
MDS1 and EVI1 Complex Locus Protein
0
MECOM protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
71-80Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK102718
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK124220
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL148012
Pays : United States
Informations de copyright
© 2021 Wiley Periodicals LLC.
Références
Swerdlow SH, Campo E, Harris NL. World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press; 2017.
Johansson B, Fioretos T, Mitelman F. Cytogenetic and molecular genetic evolution of chronic myeloid leukemia. Acta Haematol. 2002;107(2):76-94.
Ronaghy A, Hu S, Tang Z, et al. Myeloid neoplasms associated with t(3;12)(q26.2;p13) are clinically aggressive, show myelodysplasia, and frequently harbor chromosome 7 abnormalities. Mod Pathol. 2021;34(2):300-313.
Tang G, Hu S, Wang SA, et al. T(3;8)(q26.2;q24) often leads to MECOM/MYC rearrangement and is commonly associated with therapy-related myeloid neoplasms and/or disease progression. J Mol Diagn. 2019;21(2):343-351.
Tang Z, Tang G, Hu S, et al. Deciphering the complexities of MECOM rearrangement-driven chromosomal aberrations. Cancer Genet. 2019;233:21-31.
Hinai AA, Valk PJ. Review: aberrant EVI1 expression in acute myeloid leukaemia. Br J Haematol. 2016;172(6):870-878.
Lugthart S, Gröschel S, Beverloo HB, et al. Clinical, molecular, and prognostic significance of WHO type inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and various other 3q abnormalities in acute myeloid leukemia. J Clin Oncol. 2010;28(24):3890-3898.
Lugthart S, van Drunen E, van Norden Y, et al. High EVI1 levels predict adverse outcome in acute myeloid leukemia: prevalence of EVI1 overexpression and chromosome 3q26 abnormalities underestimated. Blood. 2008;111(8):4329-4337.
Haferlach C, Bacher U, Grossmann V, et al. Three novel cytogenetically cryptic EVI1 rearrangements associated with increased EVI1 expression and poor prognosis identified in 27 acute myeloid leukemia cases. Genes Chromosomes Cancer. 2012;51(12):1079-1085.
Volkert S, Schnittger S, Zenger M, Kern W, Haferlach T, Haferlach C. Amplification of EVI1 on cytogenetically cryptic double minutes as new mechanism for increased expression of EVI1. Cancer Genet. 2014;207(3):103-108.
Arber DA, Brunning RD, LeBeau MM, et al. Acute myeloid leukemia with recurrent genetic abnormalities. In: Swerdlow S, Campo E, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues; Lyon International Agency for Research on Cancer; 2017:138-139.
Yamazaki H, Suzuki M, Otsuki A, et al. A remote GATA2 hematopoietic enhancer drives leukemogenesis in inv(3)(q21;q26) by activating EVI1 expression. Cancer Cell. 2014;25(4):415-427.
Katayama S, Suzuki M, Yamaoka A, et al. GATA2 haploinsufficiency accelerates EVI1-driven leukemogenesis. Blood. 2017;130(7):908-919.
Cuenco GM, Ren R. Both AML1 and EVI1 oncogenic components are required for the cooperation of AML1/MDS1/EVI1 with BCR/ABL in the induction of acute myelogenous leukemia in mice. Oncogene. 2004;23(2):569-579.
Buonamici S, Li D, Chi Y, et al. EVI1 induces myelodysplastic syndrome in mice. J Clin Invest. 2004;114(5):713-719.
Langabeer SE, Rogers JR, Harrison G, et al. EVI1 expression in acute myeloid leukaemia. Br J Haematol. 2001;112(1):208-211.
Russell M, List A, Greenberg P, et al. Expression of EVI1 in myelodysplastic syndromes and other hematologic malignancies without 3q26 translocations. Blood. 1994;84(4):1243-1248.
Ottema S, Mulet-Lazaro R, Beverloo HB, et al. Atypical 3q26/MECOM rearrangements genocopy inv(3)/t(3;3) in acute myeloid leukemia. Blood. 2020;136(2):224-234.
International Standing Committee on Human Cytogenomic N, Shaffer LG, Schmid M, McGowan-Jordan J. ISCN: an International System for Human Cytogenomic Nomenclature (2016). Karger; 2016.
He J, Abdel-Wahab O, Nahas MK, et al. Integrated genomic DNA/RNA profiling of hematologic malignancies in the clinical setting. Blood. 2016;127(24):3004-3014.
Tang Z, Tang G, Hu S, et al. Data on MECOM rearrangement-driven chromosomal aberrations in myeloid malignancies. Data Brief. 2019;24:104025.
Summerer I, Haferlach C, Meggendorfer M, Kern W, Haferlach T, Stengel A. Prognosis of MECOM (EVI1)-rearranged MDS and AML patients rather depends on accompanying molecular mutations than on blast count. Leuk Lymphoma. 2020;61(7):1756-1759.
Lavallee VP, Gendron P, Lemieux S, D'Angelo G, Hebert J, Sauvageau G. EVI1-rearranged acute myeloid leukemias are characterized by distinct molecular alterations. Blood. 2015;125(1):140-143.
Gröschel S, Sanders MA, Hoogenboezem R, et al. Mutational spectrum of myeloid malignancies with inv(3)/t(3;3) reveals a predominant involvement of RAS/RTK signaling pathways. Blood. 2015;125(1):133-139.
Yin CC, Cortes J, Barkoh B, Hayes K, Kantarjian H, Jones D. t(3;21)(q26;q22) in myeloid leukemia: an aggressive syndrome of blast transformation associated with hydroxyurea or antimetabolite therapy. Cancer. 2006;106(8):1730-1738.
Han Q, Lu J, Wang J, et al. H2AFY is a novel fusion partner of MECOM in acute myeloid leukemia. Cancer Genet. 2018;222-223:9-12.
Capela de Matos RR, MAK O, Ferreira GM, et al. Molecular approaches identify a cryptic MECOM rearrangement in a child with a rapidly progressive myeloid neoplasm. Cancer Genet. 2018;221:25-30.
Ho TH, Charlet BN, Poulos MG, Singh G, Swanson MS, Cooper TA. Muscleblind proteins regulate alternative splicing. EMBO J. 2004;23(15):3103-3112.
Branford S, Wang P, Yeung DT, et al. Integrative genomic analysis reveals cancer-associated mutations at diagnosis of CML in patients with high-risk disease. Blood. 2018;132(9):948-961.
Reineke LC, Lloyd RE. The stress granule protein G3BP1 recruits protein kinase R to promote multiple innate immune antiviral responses. J Virol. 2015;89(5):2575-2589.