Prognostic value of cytogenetics in adult patients with Philadelphia-negative acute lymphoblastic leukemia

Gómez-Seguí, Inés; Cervera, José; Such, Esperanza; Martínez‐Cuadrón, David; Luna, Irene; Ibáñez, Mariam; López-Pavía, María; Gascón, Adriana; Roig, M. Gómez; Martínez, J. Larrauri; Sanz, Jaime; Montesinos, Pau; Martín-Aragonés, G; Lorenzo, Ignacio; Senent, Leonor; Barragán, Eva; Cordón, Lourdes; Sempere, Amparo; Sanz, Guillermo; Sanz, Miguel Á.

doi:10.1007/s00277-011-1331-z

Cited by 6 publications

(2 citation statements)

References 15 publications

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“…As a specific cytogenetic subgroup of ALL, HeH has a reported frequency of 5-10% [25][26]. The pattern observed is nonrandom; however, chromosomes X, 4, 6, 10, 14, 17, 18 and 21 are found to be the most frequently gained ones [11,14].…”

Section: Discussionmentioning

confidence: 98%

A De Novo Childhood Case of T-cell Lymphoblastic Leukemia with High Hyperdiploid Karyotype Carrying an Unreported Balanced Translocation t(X;5)(q26;q31.3~32) in A Male Patient

Wafa¹,

As'sad²,

Liehr³

et al. 2018

obm genet

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Background: The aggressive T-cell acute lymphoblastic leukemia (T-ALL) is one of the frequently occurring malignancies of the thymocytes. T-ALL is observed in 15% and 25% of all new diagnosed ALL cases in children and adults, respectively. Notably, T-ALL has a 3-fold higher incidence in males than in females. In nearly half of T-ALL cases, structural and/or numerical chromosomal abnormalities are detected, which have an important prognostic significance. A well-known genetic subtype of B-ALL, high hyperdiploidy (HeH) (51-65 chromosomes) is associated with good survival and an excellent outcome. The commonly acquired chromosomes in HeH are +4, +6, +10, +14, +17, +18, +21 and +X. However, how

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Section: Discussionmentioning

confidence: 98%

A De Novo Childhood Case of T-cell Lymphoblastic Leukemia with High Hyperdiploid Karyotype Carrying an Unreported Balanced Translocation t(X;5)(q26;q31.3~32) in A Male Patient

Wafa¹,

As'sad²,

Liehr³

et al. 2018

obm genet

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“…FLT3 mutations) have been reported to act as potential secondary hits in up to 40% of APL cases. [ 2 ] However, little is known about the nature and precise role of these cooperating events in APL [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

The Mutational Landscape of Acute Promyelocytic Leukemia Reveals an Interacting Network of Co-Occurrences and Recurrent Mutations

et al. 2016

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Preliminary Acute Promyelocytic Leukemia (APL) whole exome sequencing (WES) studies have identified a huge number of somatic mutations affecting more than a hundred different genes mainly in a non-recurrent manner, suggesting that APL is a heterogeneous disease with secondary relevant changes not yet defined. To extend our knowledge of subtle genetic alterations involved in APL that might cooperate with PML/RARA in the leukemogenic process, we performed a comprehensive analysis of somatic mutations in APL combining WES with sequencing of a custom panel of targeted genes by next-generation sequencing. To select a reduced subset of high confidence candidate driver genes, further in silico analysis were carried out. After prioritization and network analysis we found recurrent deleterious mutations in 8 individual genes (STAG2, U2AF1, SMC1A, USP9X, IKZF1, LYN, MYCBP2 and PTPN11) with a strong potential of being involved in APL pathogenesis. Our network analysis of multiple mutations provides a reliable approach to prioritize genes for additional analysis, improving our knowledge of the leukemogenesis interactome. Additionally, we have defined a functional module in the interactome of APL. The hypothesis is that the number, or the specific combinations, of mutations harbored in each patient might not be as important as the disturbance caused in biological key functions, triggered by several not necessarily recurrent mutations.

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High hyperdiploidy among adolescents and adults with acute lymphoblastic leukaemia (ALL): cytogenetic features, clinical characteristics and outcome

et al. 2013

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High hyperdiploidy (HeH, 51-65 chromosomes) is an established genetic subtype of acute lymphoblastic leukaemia (ALL). The clinical and cytogenetic features as well as outcome of HeH among adolescents and adults have not been thoroughly investigated. Among 1232 B-cell precursor ALL patients (15-65 years) treated in the UKALLXII/ECOG2993 trial, 160 (13%) had a HeH karyotype, including 80 patients aged >24 years. The frequency of HeH was the same in Philadelphia chromosome (Ph)-positive and -negative cases, but Ph-positive patients were older. The cytogenetic profiles of Ph-positive and Ph-negative HeH cases were similar, although trisomy 2 was strongly associated with Ph-positive HeH. Overall, Ph-positive HeH patients did not have an inferior overall survival compared with Ph-negative patients (P=0.2: 50 vs 57% at 5 years). Trisomy of chromosome 4 was associated with a superior outcome in Ph-negative patients, whereas +5 and +20 were associated with an inferior outcome in Ph-positive and Ph-negative patients, respectively. All three markers retained significance in multivariate analysis adjusting for age and white cell count: hazard ratio for risk of death 0.47 (95% CI: 0.27-0.84) (P=0.01), 3.73 (1.51-9.21) (P=0.004) and 2.63 (1.25-5.54) (P=0.01), respectively. In conclusion, HeH is an important subtype of ALL at all ages and displays outcome heterogeneity according to chromosomal gain.

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Prognostic value of cytogenetics in adult patients with Philadelphia-negative acute lymphoblastic leukemia

Cited by 6 publications

References 15 publications

A De Novo Childhood Case of T-cell Lymphoblastic Leukemia with High Hyperdiploid Karyotype Carrying an Unreported Balanced Translocation t(X;5)(q26;q31.3~32) in A Male Patient

A De Novo Childhood Case of T-cell Lymphoblastic Leukemia with High Hyperdiploid Karyotype Carrying an Unreported Balanced Translocation t(X;5)(q26;q31.3~32) in A Male Patient

The Mutational Landscape of Acute Promyelocytic Leukemia Reveals an Interacting Network of Co-Occurrences and Recurrent Mutations

High hyperdiploidy among adolescents and adults with acute lymphoblastic leukaemia (ALL): cytogenetic features, clinical characteristics and outcome

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