Monosomy 7 and deletion 7q in children and adolescents with acute myeloid leukemia: an international retrospective study

Hasle, Henrik; Alonzo, Todd A.; Auvrignon, Anne; Béhar, C; Chang, Myron; Creutzig, Ursula; Fischer, Alexandra; Forestier, Erik; Fynn, Alcira; Haas, Oskar A.; Harbott, Jochen; Harrison, Christine J.; Heerema, Nyla A.; Heuvel‐Eibrink, Marry M. van den; Kaspers, Gertjan J. L.; Locatelli, Franco; Noellke, Peter; Polychronopoulou, Sophia; Ravindranath, Yaddanapudi; Razzouk, Bassem I.; Reinhardt, Dirk; Savva, Natalia N.; Stark, Birgit; Suciu, Stefan; Tsukimoto, Ichiro; Webb, David; Wojcik, Dorora; Woods, William G.; Zimmermann, Martin; Niemeyer, Charlotte M.; Raimondi, Susana C.

doi:10.1182/blood-2006-10-051342

Cited by 131 publications

(87 citation statements)

References 39 publications

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“…AML patients with monosomy 7 rather than with deleted 7q chromosome were reported to lead to poor prognosis. 16 Significantly poor prognosis of À5 group in our series might be explained by the observation that À5 was significantly correlated with presence of monosomy 7 as compared to del(5q) group (Po0.001). The co-presence of chromosomes 5 and 7 abnormalities has been associated with poor outcomes in MDS and AML.…”

Section: Discussionmentioning

confidence: 57%

Myelodysplastic syndrome with chromosome 5 abnormalities: a nationwide survey in Japan

et al. 2008

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Chromosome 5 abnormalities, deletion of the long arm of chromosome 5 (del(5q)) or monosomy 5 (À5), arise in about 10% of myelodysplastic syndromes (MDS), either as the sole cytogenetic abnormality or as part of complicated karyotype, and has distinct clinical implications for MDS. However, the prognostic factors of MDS patients with chromosome 5 abnormalities are not determined yet. In this study, 183 Japanese MDS patients with chromosome 5 abnormalities were analyzed. Estimated incidence of del(5q) and 5q-syndrome among MDS patients was 8.4 and 1.3%, respectively. Significant shorter overall survival (OS) and leukemia-free survival (LFS) were observed in À5 patients than del(5q) patients. Among del(5q) patients, addition of monosomy 7 or complex karyotype with more than three abnormalities were significantly related to shorter OS.LFS of del(5q) patients was divided into two risk groups by international prognostic scoring system (IPSS): low/intermediate (Int)-1 and Int-2/high groups. LFS sorted by World Health Organization classification-based prognostic scoring system (WPSS) was also divided into two groups: very low/low/Int and high/very high, and WPSS was able to predict the outcome of del(5q) patients more clearly than IPSS.Together with additional cytogenetic data, WPSS might be useful for clinical decision making in MDS patients with del(5q).

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Section: Discussionmentioning

confidence: 57%

Myelodysplastic syndrome with chromosome 5 abnormalities: a nationwide survey in Japan

et al. 2008

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“…41 In addition, a recent report in pediatric AML patients with monosomy 7 showed a higher incidence of 3q26 rearrangements, and a role for EVI1 was already suggested by these investigators. 37 We know from Fanconi anemia that patients with 3q26 aberrations have a higher risk of developing AML and if monosomy 7 develops, this occurs in the 3q26 aberrant clone as a second event. 42 Therefore, as both MLL-AF6 and monosomy 7 are associated with poor outcome in pediatric AML, 37,38,43 this may underscore that EVI1 has a role in these leukemias.…”

Section: Discussionmentioning

confidence: 99%

“…37 We know from Fanconi anemia that patients with 3q26 aberrations have a higher risk of developing AML and if monosomy 7 develops, this occurs in the 3q26 aberrant clone as a second event. 42 Therefore, as both MLL-AF6 and monosomy 7 are associated with poor outcome in pediatric AML, 37,38,43 this may underscore that EVI1 has a role in these leukemias. However, direct evidence demonstrating an oncogenic effect of EVI1 þ overexpression in these types of leukemia could not be derived from our study and further evidence is currently lacking.…”

Section: Discussionmentioning

confidence: 99%

EVI1 overexpression in distinct subtypes of pediatric acute myeloid leukemia

et al. 2010

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Overexpression of the ecotropic virus integration-1 (EVI1) gene (EVI1 þ ), localized at chromosome 3q26, is associated with adverse outcome in adult acute myeloid leukemia (AML). In pediatric AML, 3q26 abnormalities are rare, and the role of EVI1 is unknown. We studied 228 pediatric AML samples for EVI1 þ using gene expression profiling and RQ-PCR. EVI1 þ was found in 20/213 (9%) of children with de novo AML, and in 4/8 with secondary AML. It was predominantly found in MLLrearranged AML (13/47), monosomy 7 (2/3), or FAB M6/7 (6/10), and mutually exclusive with core-binding factor AML, t(15;17), and NPM1 mutations. Fluorescent in situ hybridization (FISH) was performed to detect cryptic 3q26 abnormalities. However, none of the EVI1 þ patients harbored structural 3q26 alterations. Although significant differences in 4 years pEFS for EVI1 þ and EVI1À pediatric AML were observed (28%±11 vs 44%±4, P ¼ 0.04), multivariate analysis did not identify EVI1 þ as an independent prognostic factor. We conclude that EVI1 þ can be found in B10% of pediatric AML. Although EVI1 þ was not an independent prognostic factor, it was predominantly found in subtypes of pediatric AML that are related with an intermediate to unfavorable prognosis. Further research should explain the role of EVI1 þ in disease biology in these cases. Remarkably, no 3q26 abnormalities were identified in EVI1 þ pediatric AML.

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“…23 A total of 108 patients received allogeneic HSCT in first complete remission, whereas 59 patients underwent autologous HSCT; these patients were included in the "chemotherapy only" group. 24 …”

Section: Patientsmentioning

confidence: 99%

Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study

Balgobind

Raimondi

Harbott

et al. 2009

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Translocations involving chromosome 11q23 frequently occur in pediatric acute myeloid leukemia (AML) and are associated with poor prognosis. In most cases, the MLL gene is involved, and more than 50 translocation partners have been described. Clinical outcome data of the 11q23-rearranged subgroups are scarce because most 11q23 series are too small for meaningful analysis of subgroups, although some studies suggest that patients with t(9;11)(p22;q23) have a more favorable prognosis. We retrospectively collected outcome data of 756 children with 11q23-or MLL-rearranged AML from 11 collaborative groups to identify differences in outcome based on translocation partners. All karyotypes were centrally reviewed before assigning patients to subgroups. The event-free survival of 11q23/ MLL-rearranged pediatric AML at 5 years from diagnosis was 44% (؎ 5%), with large differences across subgroups (11% ؎ 5% to 92% ؎ 5%). Multivariate analysis identified the following subgroups as independent prognostic predictors: t(1;11)(q21;q23) (hazard ratio [HR] ‫؍‬ 0.1, P ‫؍‬ .004); t(6; 11)(q27;q23) (HR ‫؍‬ 2.2, P < .001); t(10; 11)(p12;q23) (HR ‫؍‬ 1.5, P ‫؍‬ .005); and t(10;11)(p11.2;q23) (HR ‫؍‬ 2.5, P ‫؍‬ .005). We could not confirm the favorable prognosis of the t(9;11)(p22;q23) subgroup. We identified large differences in outcome within 11q23/MLL-rearranged pediatric AML and novel subgroups based on translocation partners that independently predict clinical outcome. Screening for these translocation partners is needed for accurate treatment stratification at diagnosis. (Blood. 2009;114:2489-2496)

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Monosomy 7 and deletion 7q in children and adolescents with acute myeloid leukemia: an international retrospective study

Cited by 131 publications

References 39 publications

Myelodysplastic syndrome with chromosome 5 abnormalities: a nationwide survey in Japan

Myelodysplastic syndrome with chromosome 5 abnormalities: a nationwide survey in Japan

EVI1 overexpression in distinct subtypes of pediatric acute myeloid leukemia

Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study

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