Dataset Information

A Low Frequency of Losses in 11q Chromosome Is Associated with Better Outcome and Lower Rate of Genomic Mutations in Patients with Chronic Lymphocytic Leukemia.

ABSTRACT: To analyze the impact of the 11q deleted (11q-) cells in CLL patients on the time to first therapy (TFT) and overall survival (OS), 2,493 patients with CLL were studied. 242 patients (9.7%) had 11q-. Fluorescence in situ hybridization (FISH) studies showed a threshold of 40% of deleted cells to be optimal for showing that clinical differences in terms of TFT and OS within 11q- CLLs. In patients with ?40% of losses in 11q (11q-H) (74%), the median TFT was 19 months compared with 44 months in CLL patients with <40% del(11q) (11q-L) (P<0.0001). In the multivariate analysis, only the presence of 11q-L, mutated IGHV status, early Binet stage and absence of extended lymphadenopathy were associated with longer TFT. Patients with 11q-H had an OS of 90 months, while in the 11q-L group the OS was not reached (P = 0.008). The absence of splenomegaly (P = 0.02), low LDH (P = 0.018) or ?2M (P = 0.006), and the presence of 11q-L (P = 0.003) were associated with a longer OS. In addition, to detect the presence of mutations in the ATM, TP53, NOTCH1, SF3B1, MYD88, FBXW7, XPO1 and BIRC3 genes, a select cohort of CLL patients with losses in 11q was sequenced by next-generation sequencing of amplicons. Eighty % of CLLs with 11q- showed mutations and fewer patients with low frequencies of 11q- had mutations among genes examined (50% vs 94.1%, P = 0.023). In summary, CLL patients with <40% of 11q- had a long TFT and OS that could be associated with the presence of fewer mutated genes.

SUBMITTER: Hernandez JA

PROVIDER: S-EPMC4667902 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A Low Frequency of Losses in 11q Chromosome Is Associated with Better Outcome and Lower Rate of Genomic Mutations in Patients with Chronic Lymphocytic Leukemia.

Hernández José Ángel JÁ Hernández-Sánchez María M Rodríguez-Vicente Ana Eugenia AE Grossmann Vera V Collado Rosa R Heras Cecilia C Puiggros Anna A Martín Ana África AÁ Puig Noemí N Benito Rocío R Robledo Cristina C Delgado Julio J González Teresa T Queizán José Antonio JA Galende Josefina J de la Fuente Ignacio I Martín-Núñez Guillermo G Alonso José María JM Abrisqueta Pau P Luño Elisa E Marugán Isabel I González-Gascón Isabel I Bosch Francesc F Kohlmann Alexander A González Marcos M Espinet Blanca B Hernández-Rivas Jesús María JM Hernández-Rivas Jesús María JM

PloS one 20151202 11

To analyze the impact of the 11q deleted (11q-) cells in CLL patients on the time to first therapy (TFT) and overall survival (OS), 2,493 patients with CLL were studied. 242 patients (9.7%) had 11q-. Fluorescence in situ hybridization (FISH) studies showed a threshold of 40% of deleted cells to be optimal for showing that clinical differences in terms of TFT and OS within 11q- CLLs. In patients with ≥40% of losses in 11q (11q-H) (74%), the median TFT was 19 months compared with 44 months in CLL ...[more]

PMID: 26630574

Similar Datasets

Project description:Purpose Philadelphia chromosome (Ph) -like acute lymphoblastic leukemia (ALL) is a high-risk subtype of childhood ALL characterized by kinase-activating alterations that are amenable to treatment with tyrosine kinase inhibitors. We sought to define the prevalence and genomic landscape of Ph-like ALL in adults and assess response to conventional chemotherapy. Patients and Methods The frequency of Ph-like ALL was assessed by gene expression profiling of 798 patients with B-cell ALL age 21 to 86 years. Event-free survival and overall survival were determined for Ph-like ALL versus non-Ph-like ALL patients. Detailed genomic analysis was performed on 180 of 194 patients with Ph-like ALL. Results Patients with Ph-like ALL accounted for more than 20% of adults with ALL, including 27.9% of young adults (age 21 to 39 years), 20.4% of adults (age 40 to 59 years), and 24.0% of older adults (age 60 to 86 years). Overall, patients with Ph-like ALL had an inferior 5-year event-free survival compared with patients with non-Ph-like ALL (22.5% [95% CI, 14.9% to 29.3%; n = 155] v 49.3% [95% CI, 42.8% to 56.2%; n = 247], respectively; P < .001). We identified kinase-activating alterations in 88% of patients with Ph-like ALL, including CRLF2 rearrangements (51%), ABL class fusions (9.8%), JAK2 or EPOR rearrangements (12.4%), other JAK-STAT sequence mutations (7.2%), other kinase alterations (4.1%), and Ras pathway mutations (3.6%). Eleven new kinase rearrangements were identified, including four involving new kinase or cytokine receptor genes and seven involving new partners for previously identified genes. Conclusion Ph-like ALL is a highly prevalent subtype of ALL in adults and is associated with poor outcome. The diverse range of kinase-activating alterations in Ph-like ALL has important therapeutic implications. Trials comparing the addition of tyrosine kinase inhibitors to conventional therapy are required to evaluate the clinical utility of these agents in the treatment of Ph-like ALL.

Dataset Information

A Low Frequency of Losses in 11q Chromosome Is Associated with Better Outcome and Lower Rate of Genomic Mutations in Patients with Chronic Lymphocytic Leukemia.

Publications

A Low Frequency of Losses in 11q Chromosome Is Associated with Better Outcome and Lower Rate of Genomic Mutations in Patients with Chronic Lymphocytic Leukemia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets