High PRDM16 expression identifies a prognostic subgroup of pediatric acute myeloid leukaemia correlated to FLT3-ITD, KMT2A-PTD, and NUP98-NSD1: the results of the Japanese Paediatric Leukaemia/Lymphoma Study Group AML-05 trial

被引：43

作者：

Shiba, Norio ^{[1
,2
]}

Ohki, Kentaro ^{[1
]}

Kobayashi, Tohru ^{[3
]}

Hara, Yusuke ^{[1
,2
]}

Yamato, Genki ^{[1
,2
]}

Tanoshima, Reo ^{[4
]}

Ichikawa, Hitoshi ^{[5
]}

Tomizawa, Daisuke ^{[6
]}

Park, Myoung-ja ^{[1
]}

Shimada, Akira ^{[7
]}

Sotomatsu, Manabu ^{[1
]}

Arakawa, Hirokazu ^{[2
]}

Horibe, Keizo ^{[8
]}

Adachi, Souichi ^{[9
]}

Taga, Takashi ^{[10
]}

Tawa, Akio ^{[11
]}

Hayashi, Yasuhide ^{[1
]}

机构：

[1] Gunma Childrens Med Ctr, Dept Haematol Oncol, 779 Shimohakoda, Shibukawa, Gunma 3778577, Japan

[2] Gunma Univ, Grad Sch Med, Dept Paediat, Maebashi, Gunma 371, Japan

[3] Natl Ctr Child Hlth & Dev, Ctr Clin Res & Dev, Dept Dev Strategy, Div Clin Res Planning, Tokyo, Japan

[4] Yokohama City Univ Med, Dept Paediat, Yokohama, Kanagawa, Japan

[5] Natl Canc Ctr, Res Inst, Div Genet, Tokyo 104, Japan

[6] Natl Ctr Child Hlth & Dev, Childrens Canc Ctr, Div Leukaemia & Lymphoma, Tokyo, Japan

[7] Okayama Univ Hosp, Dept Pediat, Okayama, Japan

[8] Nagoya Med Ctr, Natl Hosp Org, Clin Res Ctr, Nagoya, Aichi, Japan

[9] Kyoto Univ, Grad Sch Med, Dept Human Hlth Sci, Kyoto, Japan

[10] Shiga Univ Med Sci, Dept Paediat, Otsu, Shiga, Japan

[11] Osaka Natl Hosp, Natl Hosp Org, Dept Paediat, Osaka, Japan

来源：

BRITISH JOURNAL OF HAEMATOLOGY | 2016年 / 172卷 / 04期

关键词：

PRDM16; FLT3-ITD; KMT2A-PTD; NUP98-NSD1; gene expression; AML; TANDEM DUPLICATIONS; DNMT3A MUTATIONS; NPM1; MUTATIONS; GENE; MLL; IMPACT; CYTARABINE; RELEVANCE; DISTINCT; THERAPY;

D O I：

10.1111/bjh.13869

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Recent reports described the NUP98-NSD1 fusion as an adverse prognostic marker for acute myeloid leukaemia (AML) and PRDM16 (also known as MEL1) as the representative overexpressed gene in patients harbouring NUP98-NSD1 fusion. PRDM16 gene expression levels were measured via real-time polymerase chain reaction in 369 paediatric patients with de novo AML, of whom 84 (23%) exhibited PRDM16 overexpression (PRDM16/ABL1 ratio 0010). The frequencies of patients with high or low PRDM16 expression differed widely with respect to each genetic alteration, as follows: t(8;21), 4% vs. 96%, P<0001; inv(16), 0% vs. 100%, P<0001; KMT2A (also termed MLL)- partial tandem duplication, 100% vs. 0%, P<0001; NUP98-NSD1, 100% vs. 0%, P<0001. The overall survival (OS) and event-free survival (EFS) among PRDM16-overexpressing patients were significantly worse than in patients with low PRDM16 expression (3-year OS: 51% vs. 81%, P<0001, 3-year EFS: 32% vs. 64%, P<0001) irrespective of other cytogenetic alterations except for NPM1. PRDM16 gene expression was particularly useful for stratifying FLT3-internal tandem duplication-positive AML patients (3-year OS: high=30% vs. low=70%, P<0001). PRDM16 overexpression was highly recurrent in de novo paediatric AML patients with high/intermediate-risk cytogenetic profiles and was independently associated with an adverse outcome.

引用

页码：581 / 591

页数：11

共 32 条

[1] Acquired mutations in the genes encoding IDH1 and IDH2 both are recurrent aberrations in acute myeloid leukemia: prevalence and prognostic value [J].

Abbas, Saman ;

Lugthart, Sanne ;

Kavelaars, Francois G. ;

Schelen, Anita ;

Koenders, Jasper E. ;

Zeilemaker, Annelieke ;

van Putten, Wim J. L. ;

Rijneveld, Anita W. ;

Lowenberg, Bob ;

Valk, Peter J. M. .

BLOOD, 2010, 116 (12) :2122-2126

[2] Low frequency of MLL-partial tandem duplications in paediatric acute myeloid leukaemia using MLPA as a novel DNA screenings technique [J].

Balgobind, Brian V. ;

Hollink, Iris H. I. M. ;

Reinhardt, Dirk ;

van Wering, Elisabeth R. ;

de Graaf, Siebold S. N. ;

Baruchel, Andre ;

Stary, Jan ;

Beverloo, H. Berna ;

de Greef, Georgine E. ;

Pieters, Rob ;

Zwaan, C. Michel ;

van den Heuvel-Eibrink, Marry M. .

EUROPEAN JOURNAL OF CANCER, 2010, 46 (10) :1892-1899

[3] Evaluation of candidate control genes for diagnosis and residual disease detection in leukemic patients using 'real-time' quantitative reverse-transcriptase polymerase chain reaction (RQ-PCR) - a Europe against cancer program [J].

Beillard, E ;

Pallisgaard, N ;

van der Velden, VHJ ;

Bi, W ;

Dee, R ;

van der Schoot, E ;

Delabesse, E ;

Macintyre, E ;

Gottardi, E ;

Saglio, G ;

Watzinger, F ;

Lion, T ;

van Dongen, JJM ;

Hokland, P ;

Gabert, J .

LEUKEMIA, 2003, 17 (12) :2474-2486

[4] Mutation in TET2 in Myeloid Cancers [J].

Delhommeau, Francois ;

Dupont, Sabrina ;

Della Valle, Veronique ;

James, Chloe ;

Trannoy, Severine ;

Masse, Aline ;

Kosmider, Olivier ;

Le Couedic, Jean-Pierre ;

Robert, Fabienne ;

Alberdi, Antonio ;

Lecluse, Yann ;

Plo, Isabelle ;

Dreyfus, Francois J. ;

Marzac, Christophe ;

Casadevall, Nicole ;

Lacombe, Catherine ;

Romana, Serge P. ;

Dessen, Philippe ;

Soulier, Jean ;

Viguie, Franck ;

Fontenay, Michaela ;

Vainchenker, William ;

Bernard, Olivier A. .

NEW ENGLAND JOURNAL OF MEDICINE, 2009, 360 (22) :2289-2301

[5] Genetics of myeloid malignancies:: Pathogenetic and clinical implications [J].

Fröhling, S ;

Scholl, C ;

Gilliland, DG ;

Levine, RL .

JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (26) :6285-6295

[6] The impact of FLT3 internal tandem duplication mutant level, number, size, and interaction with NPM1 mutations in a large cohort of young adult patients with acute myeloid leukemia [J].

Gale, Rosemary E. ;

Green, Claire ;

Allen, Christopher ;

Mead, Adam J. ;

Burnett, Alan K. ;

Hils, Robert K. ;

Linch, David C. .

BLOOD, 2008, 111 (05) :2776-2784

[7] Favorable prognostic impact of NPM1 gene mutations in childhood acute myeloid leukemia, with emphasis on cytogenetically normal AML [J].

Hollink, I. H. I. M. ;

Zwaan, C. M. ;

Zimmermann, M. ;

Arentsen-Peters, T. C. J. M. ;

Pieters, R. ;

Cloos, J. ;

Kaspers, G. J. L. ;

de Graaf, S. S. N. ;

Harbott, J. ;

Creutzig, U. ;

Reinhardt, D. ;

van den Heuvel-Eibrink, M. M. ;

Thiede, C. .

LEUKEMIA, 2009, 23 (02) :262-270

[8] NUP98/NSD1 characterizes a novel poor prognostic group in acute myeloid leukemia with a distinct HOX gene expression pattern [J].

Hollink, Iris H. I. M. ;

van den Heuvel-Eibrink, Marry M. ;

Arentsen-Peters, Susan T. C. J. M. ;

Pratcorona, Marta ;

Abbas, Saman ;

Kuipers, Jenny E. ;

van Galen, Janneke F. ;

Beverloo, H. Berna ;

Sonneveld, Edwin ;

Kaspers, Gert-Jan J. L. ;

Trka, Jan ;

Baruchel, Andre ;

Zimmermann, Martin ;

Creutzig, Ursula ;

Reinhardt, Dirk ;

Pieters, Rob ;

Valk, Peter J. M. ;

Zwaan, C. Michel .

BLOOD, 2011, 118 (13) :3645-3656

[9] High expression of EVI1 and MEL1 is a compelling poor prognostic marker of pediatric AML [J].

Jo, A. ;

Mitani, S. ;

Shiba, N. ;

Hayashi, Y. ;

Hara, Y. ;

Takahashi, H. ;

Tsukimoto, I. ;

Tawa, A. ;

Horibe, K. ;

Tomizawa, D. ;

Taga, T. ;

Adachi, S. ;

Yoshida, T. ;

Ichikawa, H. .

LEUKEMIA, 2015, 29 (05) :1076-1083

[10] Investigation of the freely available easy-to-use software 'EZR' for medical statistics [J].

Kanda, Y. .

BONE MARROW TRANSPLANTATION, 2013, 48 (03) :452-458

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