Genetic correlates in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with Hyper-CVAD plus dasatinib or ponatinib
Recurring genetic abnormalities have been identified in Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). Among them, IKZF1 deletion was associated with poor prognosis in patients treated with imatinib-based or dasatinib-based regimens. However, the molecular determinants for...
Saved in:
Published in | Leukemia Vol. 36; no. 5; pp. 1253 - 1260 |
---|---|
Main Authors | , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
01.05.2022
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Recurring genetic abnormalities have been identified in Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). Among them,
IKZF1
deletion was associated with poor prognosis in patients treated with imatinib-based or dasatinib-based regimens. However, the molecular determinants for clinical outcomes in ponatinib-treated patients remain unknown. We systematically analyzed genetic alterations in adults with Ph-positive ALL uniformly treated in clinical trials with dasatinib-based regimens or a ponatinib-based regimen and investigated the molecular determinants for treatment outcomes using pretreatment specimens collected from adults with Ph-positive ALL treated with Hyper-CVAD plus dasatinib or ponatinib. DNA sequencing and SNP microarray were performed and recurrent genetic abnormalities were found in 84% of the patients, among whom
IKZF1
deletion was most frequently detected (60%).
IKZF1
deletion frequently co-occurred with other copy-number abnormalities (
IKZF1
plus
, 46%) and was significantly associated with unfavorable overall survival (OS) (false discovery rate < 0.1) and increased cumulative incidence of relapse (
p
= 0.01). In a multivariate analysis, dasatinib therapy, lack of achievement of 3-month complete molecular response, and the presence of
IKZF1
plus
status were significantly associated with poor OS. The differential impact of
IKZF1
plus
was largely restricted to patients given Hyper-CVAD plus ponatinib; dasatinib-based regimens had unfavorable outcomes regardless of the molecular abnormalities. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0887-6924 1476-5551 |
DOI: | 10.1038/s41375-021-01496-8 |