EVI1 overexpression is a poor prognostic factor in pediatric patients with mixed lineage leukemia-AF9 rearranged acute myeloid leukemia

Matsuo, Hidemasa; Kajihara, Masako; Tomizawa, Daisuke; Watanabe, Tetsu; Saito, Akiko; Fujimoto, Junichiro; Horibe, Keizo; Kodama, K.; Tokumasu, Mayu; Itoh, Hiroshi; Nakayama, Hideki; Kinoshita, Akitoshi; Taga, Takashi; Tawa, Akio; Taki, Tomohiko; Shiba, Norio; Ohki, Kentaro; Hayashi, Yasuhide; Yamashita, Yuka; Shimada, Akira; Tanaka, Shiro; Adachi, Souichi

doi:10.3324/haematol.2014.107128

Cited by 35 publications

(27 citation statements)

References 14 publications

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“…One possibility is that the older group more frequently has co‐occurring adverse genetic abnormalities than the younger group. High MECOM (previously termed EVI1 ) expression, which was reported as a poor prognostic factor in KMT2A ‐R–positive AML, was frequently found in older paediatric patients (median age: high MECOM 6·6 years vs low MECOM 4·5 years, P = 0·03) (Matsuo et al , ). Moreover, a recent study on paediatric acute lymphoblastic leukaemia with KMT2A‐R has reported a lower frequency of gene mutations in infants than older paediatric patients (1·3 vs 6·5 mutations/patient) (Andersson et al , ).…”

Section: Discussionmentioning

confidence: 99%

Patients aged less than 3 years with acute myeloid leukaemia characterize a molecularly and clinically distinct subgroup

et al. 2019

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Summary Although infants (age <1 year) with acute myeloid leukaemia (AML) have unique characteristics and are vulnerable to chemotherapy, children aged 1–2 years with AML may have characteristics similar to that of infants. Thus, we analysed 723 paediatric AML patients treated on the Japanese AML99 and AML‐05 trials to identify characteristics of younger children. We identified patients aged <3 years (the younger group) as a distinct subgroup. KMT2A‐rearrangement (KMT2A‐R), CBFA2T3‐GLIS2, CBFB‐MYH11 and NUP98‐KDM5A were frequently found in the younger group. Prognostic analyses revealed poor 5‐year overall survival (OS), event‐free survival (EFS) and cumulative incidence of relapse (CIR) in patients with CBFA2T3‐GLIS2 (42%, 17% and 83%, respectively) and those with NUP98‐KDM5A (33%, 17% and 83%, respectively). Additionally, we identified KMT2A‐R and CBFB‐MYH11 as age‐specific prognostic markers. Regarding KMT2A‐R, the younger group had significantly better OS, EFS and CIR than the older group (aged 3 to <18 years) (P = 0·023, 0·011 and <0·001, respectively). Conversely, concerning CBFB‐MYH11, the younger group had significantly poor EFS and CIR than the older group (each P < 0·001), suggesting that certain molecular markers are linked to different prognoses according to age. Therefore, we characterized patients <3 years as a distinct subgroup of paediatric AML.

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Section: Discussionmentioning

confidence: 99%

Patients aged less than 3 years with acute myeloid leukaemia characterize a molecularly and clinically distinct subgroup

et al. 2019

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“…In addition to the three fusion genes already listed, we analyzed MLL(KMT2A)‐AF9(MLLT3) , MLL‐ELL , MLL‐AF6(MLLT4) , FUS(TLS)‐ERG , and NUP98‐HOXA9 (caused by t(9;11)(p22;q23), t(11;19)(q23;p13.1), t(6;11)(q27;q23), t(16;21)(p11.2;q22), and t(7;11)(p15;p15), respectively), based on their frequency and clinical importance in pediatric AML. MLL‐AF9 is the most frequent translocation in pediatric MLL ‐rearranged AML and, although patients with MLL‐AF9 are categorized into an intermediate risk group, this subgroup may be effectively risk‐stratified based on EVI1 expression . MLL‐ELL and MLL‐AF6 are also common translocations, and MLL‐AF6 is associated with poor prognosis .…”

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confidence: 99%

Multiplex fusion gene testing in pediatric acute myeloid leukemia

Iijima-Yamashita

Matsuo

Yamada

et al. 2018

Pediatrics International

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Background: Gene abnormalities, particularly chromosome rearrangements generating gene fusion, are associated with clinical characteristics and prognosis in pediatric acute myeloid leukemia (AML). Karyotyping is generally performed to enable risk stratification, but the results are not always consistent with those of reverse transcriptionpolymerase chain reaction (RT-PCR), and more accurate and rapid methods are required.Methods: A total of 487 samples from de novo AML patients enrolled in the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML-05 study (n = 448), and from acute promyelocytic leukemia (APL) patients enrolled in the JPLSG AML-P05 study (n = 39) were available for this investigation. Multiplex quantitative RT-PCR was performed to detect eight important fusion genes: MLL-ELL, MLL-AF6(MLLT4), FUS(TLS)-ERG, NUP98-HOXA9, and PML-RARA.Results: Fusion genes were detected in 207 (46.2%) of the 448 AML-05 patient samples. After exclusion of two samples with PML-RARA, no chromosomal abnormalities were identified on karyotyping in 19 of 205 patients (9.3%) positive for fusion genes on RT-PCR. Fusion genes were confirmed on fluorescence in situ hybridization (FISH) in 11 of these 19 patients. In contrast, fusion genes were detected in 37 of 39 patients (94.9%) from the AML-P05 study, and 33 of these results were consistent with the karyotyping. There were discrepancies in four patients (10.8%), three with normal karyotypes and one in whom karyotyping was not possible. All four of these patients were PML-RARA positive on FISH.Conclusions: Multiplex quantitative RT-PCR-based fusion gene screening may be effective for diagnosis of pediatric AML.

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“…In a recent issue of Haematologica, Matsuo et al 1 pinpoint the pejorative effect of EVI1 overexpression in 18 acute myeloid leukemias (AML) with MLL rearrangements. However, EVI1 overexpression has also been reported in patients with translocations involving chromosome 3 and the EVI1 gene.…”

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“…Marion Eveillard, 1 Jacques Delaunay, 2 Steven Richebourg, 1,3 Laurence Lodé, 1 Richard Garand, 1 Soraya Wuillème, 1 François Duhoux, 4 Hélène Antoine-Poirel, 4 Catherine Godon, 1 and Marie C. Béné…”

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The closely related rare and severe acute myeloid leukemias carrying EVI1 or PRDM16 rearrangements share singular biological features

Eveillard

Delaunay²,

Richebourg

et al. 2015

Haematologica

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EVI1 overexpression is a poor prognostic factor in pediatric patients with mixed lineage leukemia-AF9 rearranged acute myeloid leukemia

Cited by 35 publications

References 14 publications

Patients aged less than 3 years with acute myeloid leukaemia characterize a molecularly and clinically distinct subgroup

Patients aged less than 3 years with acute myeloid leukaemia characterize a molecularly and clinically distinct subgroup

Multiplex fusion gene testing in pediatric acute myeloid leukemia

The closely related rare and severe acute myeloid leukemias carrying EVI1 or PRDM16 rearrangements share singular biological features

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