Tyrosine kinase inhibitor response of ABL-class acute lymphoblastic leukemia: the role of kinase type and SH3 domain.
Blood
; 143(21): 2178-2189, 2024 May 23.
Article
in En
| MEDLINE
| ID: mdl-38394665
ABSTRACT
ABSTRACT Acute lymphoblastic leukemia (ALL) with fusions of ABL-class tyrosine kinase genes other than BCRABL1 occurs in â¼3% of children with ALL. The tyrosine kinase genes involved in this BCRABL1-like (Ph-like) subtype include ABL1, PDGFRB, ABL2, and CSF1R, each of which has up to 10 described partner genes. ABL-class ALL resembles BCRABL1-positive ALL with a similar gene expression profile, poor response to chemotherapy, and sensitivity to tyrosine kinase inhibitors (TKIs). There is a lack of comprehensive data regarding TKI sensitivity in the heterogeneous group of ABL-class ALL. We observed variability in TKI sensitivity within and among each ABL-class tyrosine kinase gene subgroup. We showed that ALL samples with fusions for any of the 4 tyrosine kinase genes were relatively sensitive to imatinib. In contrast, the PDGFRB-fused ALL samples were less sensitive to dasatinib and bosutinib. Variation in ex vivo TKI response within the subset of samples with the same ABL-class tyrosine kinase gene was not associated with the ALL immunophenotype, 5' fusion partner, presence or absence of Src-homology-2/3 domains, or deletions of IKZF1, PAX5, or CDKN2A/B. In conclusion, the tyrosine kinase gene involved in ABL-class ALL is the main determinant of TKI sensitivity and relevant for specific TKI selection.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Proto-Oncogene Proteins c-abl
/
Src Homology Domains
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Protein Kinase Inhibitors
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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Limits:
Adolescent
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Child
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Child, preschool
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Female
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Humans
/
Male
Language:
En
Journal:
Blood
Year:
2024
Document type:
Article
Affiliation country:
Países Bajos
Country of publication:
Estados Unidos