Abstract
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 ≥0·010). 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 <0·001; inv(16), 0% vs. 100%, P <0·001; KMT2A (also termed MLL)- partial tandem duplication, 100% vs. 0%, P <0·001; NUP98-NSD1, 100% vs. 0%, P <0·001. 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 <0·001, 3-year EFS: 32% vs. 64%, P <0·001) 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 <0·001). 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.
| Original language | English |
|---|---|
| Pages (from-to) | 581-591 |
| Number of pages | 11 |
| Journal | British Journal of Haematology |
| Volume | 172 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Feb 1 2016 |
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Keywords
- AML
- NUP98-NSD1
- FLT3-ITD
- Gene expression
- KMT2A-PTD
- PRDM16
ASJC Scopus subject areas
- Hematology
Cite this
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. / Shiba, Norio; Ohki, Kentaro; Kobayashi, Tohru; Hara, Yusuke; Yamato, Genki; Tanoshima, Reo; Ichikawa, Hitoshi; Tomizawa, Daisuke; Park, Myoung Ja; Shimada, Akira; Sotomatsu, Manabu; Arakawa, Hirokazu; Horibe, Keizo; Adachi, Souichi; Taga, Takashi; Tawa, Akio; Hayashi, Yasuhide.
In: British Journal of Haematology, Vol. 172, No. 4, 01.02.2016, p. 581-591.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - High PRDM16 expression identifies a prognostic subgroup of pediatric acute myeloid leukaemia correlated to FLT3-ITD, KMT2A-PTD, and NUP98-NSD1
T2 - The results of the Japanese Paediatric Leukaemia/Lymphoma Study Group AML-05 trial
AU - Shiba, Norio
AU - Ohki, Kentaro
AU - Kobayashi, Tohru
AU - Hara, Yusuke
AU - Yamato, Genki
AU - Tanoshima, Reo
AU - Ichikawa, Hitoshi
AU - Tomizawa, Daisuke
AU - Park, Myoung Ja
AU - Shimada, Akira
AU - Sotomatsu, Manabu
AU - Arakawa, Hirokazu
AU - Horibe, Keizo
AU - Adachi, Souichi
AU - Taga, Takashi
AU - Tawa, Akio
AU - Hayashi, Yasuhide
PY - 2016/2/1
Y1 - 2016/2/1
N2 - 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 ≥0·010). 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 <0·001; inv(16), 0% vs. 100%, P <0·001; KMT2A (also termed MLL)- partial tandem duplication, 100% vs. 0%, P <0·001; NUP98-NSD1, 100% vs. 0%, P <0·001. 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 <0·001, 3-year EFS: 32% vs. 64%, P <0·001) 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 <0·001). 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.
AB - 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 ≥0·010). 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 <0·001; inv(16), 0% vs. 100%, P <0·001; KMT2A (also termed MLL)- partial tandem duplication, 100% vs. 0%, P <0·001; NUP98-NSD1, 100% vs. 0%, P <0·001. 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 <0·001, 3-year EFS: 32% vs. 64%, P <0·001) 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 <0·001). 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.
KW - AML
KW - NUP98-NSD1
KW - FLT3-ITD
KW - Gene expression
KW - KMT2A-PTD
KW - PRDM16
UR - http://www.scopus.com/inward/record.url?scp=84956912084&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84956912084&partnerID=8YFLogxK
U2 - 10.1111/bjh.13869
DO - 10.1111/bjh.13869
M3 - Article
C2 - 26684393
AN - SCOPUS:84956912084
VL - 172
SP - 581
EP - 591
JO - British Journal of Haematology
JF - British Journal of Haematology
SN - 0007-1048
IS - 4
ER -