Prognostic relevance of integrated genetic profiling in adult T-cell leukemia/lymphoma

Publication Date:
2018-01-12
Publisher:
American Society of Hematology (ASH)
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
Medicine
Keywords:
Lymphoid Neoplasia, Clinical Trials and Observations
Published by:
http://www.hematology.org/
_version_ 1836398746192052224
autor Kataoka, K., Iwanaga, M., Yasunaga, J.-i., Nagata, Y., Kitanaka, A., Kameda, T., Yoshimitsu, M., Shiraishi, Y., Sato-Otsubo, A., Sanada, M., Chiba, K., Tanaka, H., Ochi, Y., Aoki, K., Suzuki, H., Shiozawa, Y., Yoshizato, T., Sato, Y., Yoshida, K., Nosaka, K., Hishizawa, M., Itonaga, H., Imaizumi, Y., Munakata, W., Shide, K., Kubuki, Y., Hidaka, T., Nakamaki, T., Ishiyama, K., Miyawaki, S., Ishii, R., Nureki, O., Tobinai, K., Miyazaki, Y., Takaori-Kondo, A., Shibata, T., Miyano, S., Ishitsuka, K., Utsunomiya, A., Shimoda, K., Matsuoka, M., Watanabe, T., Ogawa, S.
beschreibung Adult T-cell leukemia/lymphoma (ATL) is a heterogeneous group of peripheral T-cell malignancies characterized by human T-cell leukemia virus type-1 infection, whose genetic profile has recently been fully investigated. However, it is still poorly understood how these alterations affect clinical features and prognosis. We investigated the effects of genetic alterations commonly found in ATL on disease phenotypes and clinical outcomes, based on genotyping data obtained from 414 and 463 ATL patients using targeted-capture sequencing and single nucleotide polymorphism array karyotyping, respectively. Aggressive (acute/lymphoma) subtypes were associated with an increased burden of genetic and epigenetic alterations, higher frequencies of TP53 and IRF4 mutations, and many copy number alterations (CNAs), including PD-L1 amplifications and CDKN2A deletions, compared with indolent (chronic/smoldering) subtypes. By contrast, STAT3 mutations were more characteristic of indolent ATL. Higher numbers of somatic mutations and CNAs significantly correlated with worse survival. In a multivariate analysis incorporating both clinical factors and genetic alterations, the Japan Clinical Oncology Group prognostic index high-risk, older age, PRKCB mutations, and PD-L1 amplifications were independent poor prognostic factors in aggressive ATL. In indolent ATL, IRF4 mutations, PD-L1 amplifications, and CDKN2A deletions were significantly associated with shorter survival, although the chronic subtype with unfavorable clinical factors was only marginally significant. Thus, somatic alterations characterizing aggressive diseases predict worse prognosis in indolent ATL, among which PD-L1 amplifications are a strong genetic predictor in both aggressive and indolent ATL. ATL subtypes are further classified into molecularly distinct subsets with different prognosis. Genetic profiling might contribute to improved prognostication and management of ATL patients.
citation_standardnr 6136851
datenlieferant ipn_articles
feed_id 310
feed_publisher American Society of Hematology (ASH)
feed_publisher_url http://www.hematology.org/
insertion_date 2018-01-12
journaleissn 1528-0020
journalissn 0006-4971
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher American Society of Hematology (ASH)
quelle Blood
relation http://www.bloodjournal.org/cgi/content/short/131/2/215?rss=1
schlagwort Lymphoid Neoplasia, Clinical Trials and Observations
search_space articles
shingle_author_1 Kataoka, K., Iwanaga, M., Yasunaga, J.-i., Nagata, Y., Kitanaka, A., Kameda, T., Yoshimitsu, M., Shiraishi, Y., Sato-Otsubo, A., Sanada, M., Chiba, K., Tanaka, H., Ochi, Y., Aoki, K., Suzuki, H., Shiozawa, Y., Yoshizato, T., Sato, Y., Yoshida, K., Nosaka, K., Hishizawa, M., Itonaga, H., Imaizumi, Y., Munakata, W., Shide, K., Kubuki, Y., Hidaka, T., Nakamaki, T., Ishiyama, K., Miyawaki, S., Ishii, R., Nureki, O., Tobinai, K., Miyazaki, Y., Takaori-Kondo, A., Shibata, T., Miyano, S., Ishitsuka, K., Utsunomiya, A., Shimoda, K., Matsuoka, M., Watanabe, T., Ogawa, S.
shingle_author_2 Kataoka, K., Iwanaga, M., Yasunaga, J.-i., Nagata, Y., Kitanaka, A., Kameda, T., Yoshimitsu, M., Shiraishi, Y., Sato-Otsubo, A., Sanada, M., Chiba, K., Tanaka, H., Ochi, Y., Aoki, K., Suzuki, H., Shiozawa, Y., Yoshizato, T., Sato, Y., Yoshida, K., Nosaka, K., Hishizawa, M., Itonaga, H., Imaizumi, Y., Munakata, W., Shide, K., Kubuki, Y., Hidaka, T., Nakamaki, T., Ishiyama, K., Miyawaki, S., Ishii, R., Nureki, O., Tobinai, K., Miyazaki, Y., Takaori-Kondo, A., Shibata, T., Miyano, S., Ishitsuka, K., Utsunomiya, A., Shimoda, K., Matsuoka, M., Watanabe, T., Ogawa, S.
shingle_author_3 Kataoka, K., Iwanaga, M., Yasunaga, J.-i., Nagata, Y., Kitanaka, A., Kameda, T., Yoshimitsu, M., Shiraishi, Y., Sato-Otsubo, A., Sanada, M., Chiba, K., Tanaka, H., Ochi, Y., Aoki, K., Suzuki, H., Shiozawa, Y., Yoshizato, T., Sato, Y., Yoshida, K., Nosaka, K., Hishizawa, M., Itonaga, H., Imaizumi, Y., Munakata, W., Shide, K., Kubuki, Y., Hidaka, T., Nakamaki, T., Ishiyama, K., Miyawaki, S., Ishii, R., Nureki, O., Tobinai, K., Miyazaki, Y., Takaori-Kondo, A., Shibata, T., Miyano, S., Ishitsuka, K., Utsunomiya, A., Shimoda, K., Matsuoka, M., Watanabe, T., Ogawa, S.
shingle_author_4 Kataoka, K., Iwanaga, M., Yasunaga, J.-i., Nagata, Y., Kitanaka, A., Kameda, T., Yoshimitsu, M., Shiraishi, Y., Sato-Otsubo, A., Sanada, M., Chiba, K., Tanaka, H., Ochi, Y., Aoki, K., Suzuki, H., Shiozawa, Y., Yoshizato, T., Sato, Y., Yoshida, K., Nosaka, K., Hishizawa, M., Itonaga, H., Imaizumi, Y., Munakata, W., Shide, K., Kubuki, Y., Hidaka, T., Nakamaki, T., Ishiyama, K., Miyawaki, S., Ishii, R., Nureki, O., Tobinai, K., Miyazaki, Y., Takaori-Kondo, A., Shibata, T., Miyano, S., Ishitsuka, K., Utsunomiya, A., Shimoda, K., Matsuoka, M., Watanabe, T., Ogawa, S.
shingle_catch_all_1 Prognostic relevance of integrated genetic profiling in adult T-cell leukemia/lymphoma
Lymphoid Neoplasia, Clinical Trials and Observations
Adult T-cell leukemia/lymphoma (ATL) is a heterogeneous group of peripheral T-cell malignancies characterized by human T-cell leukemia virus type-1 infection, whose genetic profile has recently been fully investigated. However, it is still poorly understood how these alterations affect clinical features and prognosis. We investigated the effects of genetic alterations commonly found in ATL on disease phenotypes and clinical outcomes, based on genotyping data obtained from 414 and 463 ATL patients using targeted-capture sequencing and single nucleotide polymorphism array karyotyping, respectively. Aggressive (acute/lymphoma) subtypes were associated with an increased burden of genetic and epigenetic alterations, higher frequencies of TP53 and IRF4 mutations, and many copy number alterations (CNAs), including PD-L1 amplifications and CDKN2A deletions, compared with indolent (chronic/smoldering) subtypes. By contrast, STAT3 mutations were more characteristic of indolent ATL. Higher numbers of somatic mutations and CNAs significantly correlated with worse survival. In a multivariate analysis incorporating both clinical factors and genetic alterations, the Japan Clinical Oncology Group prognostic index high-risk, older age, PRKCB mutations, and PD-L1 amplifications were independent poor prognostic factors in aggressive ATL. In indolent ATL, IRF4 mutations, PD-L1 amplifications, and CDKN2A deletions were significantly associated with shorter survival, although the chronic subtype with unfavorable clinical factors was only marginally significant. Thus, somatic alterations characterizing aggressive diseases predict worse prognosis in indolent ATL, among which PD-L1 amplifications are a strong genetic predictor in both aggressive and indolent ATL. ATL subtypes are further classified into molecularly distinct subsets with different prognosis. Genetic profiling might contribute to improved prognostication and management of ATL patients.
Kataoka, K., Iwanaga, M., Yasunaga, J.-i., Nagata, Y., Kitanaka, A., Kameda, T., Yoshimitsu, M., Shiraishi, Y., Sato-Otsubo, A., Sanada, M., Chiba, K., Tanaka, H., Ochi, Y., Aoki, K., Suzuki, H., Shiozawa, Y., Yoshizato, T., Sato, Y., Yoshida, K., Nosaka, K., Hishizawa, M., Itonaga, H., Imaizumi, Y., Munakata, W., Shide, K., Kubuki, Y., Hidaka, T., Nakamaki, T., Ishiyama, K., Miyawaki, S., Ishii, R., Nureki, O., Tobinai, K., Miyazaki, Y., Takaori-Kondo, A., Shibata, T., Miyano, S., Ishitsuka, K., Utsunomiya, A., Shimoda, K., Matsuoka, M., Watanabe, T., Ogawa, S.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_catch_all_2 Prognostic relevance of integrated genetic profiling in adult T-cell leukemia/lymphoma
Lymphoid Neoplasia, Clinical Trials and Observations
Adult T-cell leukemia/lymphoma (ATL) is a heterogeneous group of peripheral T-cell malignancies characterized by human T-cell leukemia virus type-1 infection, whose genetic profile has recently been fully investigated. However, it is still poorly understood how these alterations affect clinical features and prognosis. We investigated the effects of genetic alterations commonly found in ATL on disease phenotypes and clinical outcomes, based on genotyping data obtained from 414 and 463 ATL patients using targeted-capture sequencing and single nucleotide polymorphism array karyotyping, respectively. Aggressive (acute/lymphoma) subtypes were associated with an increased burden of genetic and epigenetic alterations, higher frequencies of TP53 and IRF4 mutations, and many copy number alterations (CNAs), including PD-L1 amplifications and CDKN2A deletions, compared with indolent (chronic/smoldering) subtypes. By contrast, STAT3 mutations were more characteristic of indolent ATL. Higher numbers of somatic mutations and CNAs significantly correlated with worse survival. In a multivariate analysis incorporating both clinical factors and genetic alterations, the Japan Clinical Oncology Group prognostic index high-risk, older age, PRKCB mutations, and PD-L1 amplifications were independent poor prognostic factors in aggressive ATL. In indolent ATL, IRF4 mutations, PD-L1 amplifications, and CDKN2A deletions were significantly associated with shorter survival, although the chronic subtype with unfavorable clinical factors was only marginally significant. Thus, somatic alterations characterizing aggressive diseases predict worse prognosis in indolent ATL, among which PD-L1 amplifications are a strong genetic predictor in both aggressive and indolent ATL. ATL subtypes are further classified into molecularly distinct subsets with different prognosis. Genetic profiling might contribute to improved prognostication and management of ATL patients.
Kataoka, K., Iwanaga, M., Yasunaga, J.-i., Nagata, Y., Kitanaka, A., Kameda, T., Yoshimitsu, M., Shiraishi, Y., Sato-Otsubo, A., Sanada, M., Chiba, K., Tanaka, H., Ochi, Y., Aoki, K., Suzuki, H., Shiozawa, Y., Yoshizato, T., Sato, Y., Yoshida, K., Nosaka, K., Hishizawa, M., Itonaga, H., Imaizumi, Y., Munakata, W., Shide, K., Kubuki, Y., Hidaka, T., Nakamaki, T., Ishiyama, K., Miyawaki, S., Ishii, R., Nureki, O., Tobinai, K., Miyazaki, Y., Takaori-Kondo, A., Shibata, T., Miyano, S., Ishitsuka, K., Utsunomiya, A., Shimoda, K., Matsuoka, M., Watanabe, T., Ogawa, S.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_catch_all_3 Prognostic relevance of integrated genetic profiling in adult T-cell leukemia/lymphoma
Lymphoid Neoplasia, Clinical Trials and Observations
Adult T-cell leukemia/lymphoma (ATL) is a heterogeneous group of peripheral T-cell malignancies characterized by human T-cell leukemia virus type-1 infection, whose genetic profile has recently been fully investigated. However, it is still poorly understood how these alterations affect clinical features and prognosis. We investigated the effects of genetic alterations commonly found in ATL on disease phenotypes and clinical outcomes, based on genotyping data obtained from 414 and 463 ATL patients using targeted-capture sequencing and single nucleotide polymorphism array karyotyping, respectively. Aggressive (acute/lymphoma) subtypes were associated with an increased burden of genetic and epigenetic alterations, higher frequencies of TP53 and IRF4 mutations, and many copy number alterations (CNAs), including PD-L1 amplifications and CDKN2A deletions, compared with indolent (chronic/smoldering) subtypes. By contrast, STAT3 mutations were more characteristic of indolent ATL. Higher numbers of somatic mutations and CNAs significantly correlated with worse survival. In a multivariate analysis incorporating both clinical factors and genetic alterations, the Japan Clinical Oncology Group prognostic index high-risk, older age, PRKCB mutations, and PD-L1 amplifications were independent poor prognostic factors in aggressive ATL. In indolent ATL, IRF4 mutations, PD-L1 amplifications, and CDKN2A deletions were significantly associated with shorter survival, although the chronic subtype with unfavorable clinical factors was only marginally significant. Thus, somatic alterations characterizing aggressive diseases predict worse prognosis in indolent ATL, among which PD-L1 amplifications are a strong genetic predictor in both aggressive and indolent ATL. ATL subtypes are further classified into molecularly distinct subsets with different prognosis. Genetic profiling might contribute to improved prognostication and management of ATL patients.
Kataoka, K., Iwanaga, M., Yasunaga, J.-i., Nagata, Y., Kitanaka, A., Kameda, T., Yoshimitsu, M., Shiraishi, Y., Sato-Otsubo, A., Sanada, M., Chiba, K., Tanaka, H., Ochi, Y., Aoki, K., Suzuki, H., Shiozawa, Y., Yoshizato, T., Sato, Y., Yoshida, K., Nosaka, K., Hishizawa, M., Itonaga, H., Imaizumi, Y., Munakata, W., Shide, K., Kubuki, Y., Hidaka, T., Nakamaki, T., Ishiyama, K., Miyawaki, S., Ishii, R., Nureki, O., Tobinai, K., Miyazaki, Y., Takaori-Kondo, A., Shibata, T., Miyano, S., Ishitsuka, K., Utsunomiya, A., Shimoda, K., Matsuoka, M., Watanabe, T., Ogawa, S.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_catch_all_4 Prognostic relevance of integrated genetic profiling in adult T-cell leukemia/lymphoma
Lymphoid Neoplasia, Clinical Trials and Observations
Adult T-cell leukemia/lymphoma (ATL) is a heterogeneous group of peripheral T-cell malignancies characterized by human T-cell leukemia virus type-1 infection, whose genetic profile has recently been fully investigated. However, it is still poorly understood how these alterations affect clinical features and prognosis. We investigated the effects of genetic alterations commonly found in ATL on disease phenotypes and clinical outcomes, based on genotyping data obtained from 414 and 463 ATL patients using targeted-capture sequencing and single nucleotide polymorphism array karyotyping, respectively. Aggressive (acute/lymphoma) subtypes were associated with an increased burden of genetic and epigenetic alterations, higher frequencies of TP53 and IRF4 mutations, and many copy number alterations (CNAs), including PD-L1 amplifications and CDKN2A deletions, compared with indolent (chronic/smoldering) subtypes. By contrast, STAT3 mutations were more characteristic of indolent ATL. Higher numbers of somatic mutations and CNAs significantly correlated with worse survival. In a multivariate analysis incorporating both clinical factors and genetic alterations, the Japan Clinical Oncology Group prognostic index high-risk, older age, PRKCB mutations, and PD-L1 amplifications were independent poor prognostic factors in aggressive ATL. In indolent ATL, IRF4 mutations, PD-L1 amplifications, and CDKN2A deletions were significantly associated with shorter survival, although the chronic subtype with unfavorable clinical factors was only marginally significant. Thus, somatic alterations characterizing aggressive diseases predict worse prognosis in indolent ATL, among which PD-L1 amplifications are a strong genetic predictor in both aggressive and indolent ATL. ATL subtypes are further classified into molecularly distinct subsets with different prognosis. Genetic profiling might contribute to improved prognostication and management of ATL patients.
Kataoka, K., Iwanaga, M., Yasunaga, J.-i., Nagata, Y., Kitanaka, A., Kameda, T., Yoshimitsu, M., Shiraishi, Y., Sato-Otsubo, A., Sanada, M., Chiba, K., Tanaka, H., Ochi, Y., Aoki, K., Suzuki, H., Shiozawa, Y., Yoshizato, T., Sato, Y., Yoshida, K., Nosaka, K., Hishizawa, M., Itonaga, H., Imaizumi, Y., Munakata, W., Shide, K., Kubuki, Y., Hidaka, T., Nakamaki, T., Ishiyama, K., Miyawaki, S., Ishii, R., Nureki, O., Tobinai, K., Miyazaki, Y., Takaori-Kondo, A., Shibata, T., Miyano, S., Ishitsuka, K., Utsunomiya, A., Shimoda, K., Matsuoka, M., Watanabe, T., Ogawa, S.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_title_1 Prognostic relevance of integrated genetic profiling in adult T-cell leukemia/lymphoma
shingle_title_2 Prognostic relevance of integrated genetic profiling in adult T-cell leukemia/lymphoma
shingle_title_3 Prognostic relevance of integrated genetic profiling in adult T-cell leukemia/lymphoma
shingle_title_4 Prognostic relevance of integrated genetic profiling in adult T-cell leukemia/lymphoma
timestamp 2025-06-30T23:31:58.128Z
titel Prognostic relevance of integrated genetic profiling in adult T-cell leukemia/lymphoma
titel_suche Prognostic relevance of integrated genetic profiling in adult T-cell leukemia/lymphoma
topic W
WW-YZ
uid ipn_articles_6136851