Distinctive genomic features of human T-lymphotropic virus type 1-related adult T-cell leukemia-lymphoma in Western populations.

Autor:	Myers CS; Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois., Williams E; University of Virginia School of Medicine, Charlottesville, Virginia., Cornejo CB; Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru., Pongas G; University of Miami, Miami, Florida., Toomey NL; University of Miami, Miami, Florida., Sanches JA; Universidade de São Paolo, São Paolo., Battistella M; Université de Paris, Paris., Mo S; Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago,Illinois., Pulitzer M; Memorial Sloan-Kettering Cancer Center, New York, New York, USA; New York-Presbyterian Hospital, New York, New York., Moskaluk CA; University of Virginia School of Medicine, Charlottesville, Virginia., Bhagat G; New York-Presbyterian Hospital, New York, New York, USA; Columbia University School of Medicine, New York, New York., Ofori K; Columbia University School of Medicine, New York, New York., Davick JJ; University of Iowa, Iowa City, Iowa., Servitje O; Hospital Universitari de Bellvitge, Barcelona., Miyashiro D; Universidade de São Paolo, São Paolo., Climent F; Hospital Universitari de Bellvitge, Barcelona., Ringbloom K; Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago,Illinois., Duenas D; Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru., Law C; Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago,Illinois., Zambrano SC; Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru., Malpica L; University of Texas MD Anderson Cancer Center, Houston, Texas., Beltran BE; Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru., Castro D; Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru., Barreto L; University of Miami, Miami, Florida, USA; Instituto Nacional de Câncer José Alencar Gomes da Silva, Rio de Janeiro., Brites C; Federal University of Bahia, Salvador., Chapman JR; University of Miami, Miami, Florida., Choi J; Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago,Illinois., Gru AA; University of Virginia School of Medicine, Charlottesville, Virginia. aag2222@cumc.columbia.edu., Ramos JC; University of Miami, Miami, Florida.
Jazyk:	angličtina
Zdroj:	Haematologica [Haematologica] 2024 Dec 01; Vol. 109 (12), pp. 4021-4039. Date of Electronic Publication: 2024 Dec 01.
DOI:	10.3324/haematol.2024.285233
Abstrakt:	Adult T-cell leukemia-lymphoma (ATLL) is an aggressive malignancy driven by human T-cell leukemia virus type 1 (HTLV-1). Although patients from the Western hemisphere (Afro-Caribbean and South American) face worse prognoses, our understanding of ATLL molecular drivers derives mostly from Japanese studies. We performed multi-omic analyses to elucidate the genomic landscape of ATLL in Western cohorts. Recurrent deletions and/or damaging mutations involving FOXO3, ANKRD11, DGKZ, and PTPN6 implicate these genes as potential tumor suppressors. RNA-sequencing, published functional data and in vitro assays support the roles of ANKRD11 and FOXO3 as regulators of T-cell proliferation and apoptosis in ATLL, respectively. Survival data suggest that ANKRD11 mutation may confer a worse prognosis. Japanese and Western cohorts, in addition to acute and lymphomatous subtypes, demonstrated distinct molecular patterns. GATA3 deletion was associated with chronic cases with unfavorable outcomes. IRF4 and CARD11 mutations frequently emerged in relapses after interferon therapy. Our findings reveal novel putative ATLL driver genes and clinically relevant differences between Japanese and Western ATLL patients.
Databáze:	MEDLINE
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