Correlation between deletion of the CDKN2 gene and tyrosine kinase inhibitor resistance in adult Philadelphia chromosome-positive acute lymphoblastic leukemia

Frequency relapses are common in Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL) following tyrosine kinase inhibitors (TKIs). CDKN2A/B is believed to contribute to this chemotherapy resistance. To further investigate the association between CDKN2 status and TKI resi...

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Published in:Journal of hematology and oncology 2016-04, Vol.9 (40), p.40-40, Article 40
Main Authors: Xu, Na, Li, Yu-ling, Li, Xuan, Zhou, Xuan, Cao, Rui, Li, Huan, Li, Lin, Lu, Zi-yuan, Huang, Ji-xian, Fan, Zhi-ping, Huang, Fen, Zhou, Hong-sheng, Zhang, Song, Liu, Zhi, Zhu, Hong-qian, Liu, Qi-fa, Liu, Xiao-li
Format: Article
Language:English
Subjects:
Acute lymphoblastic leukemia
Acute lymphocytic leukemia
Adolescent
Adult
Aged
Antigens, CD20 - genetics
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Bone marrow
Cancer
Care and treatment
CD20
CDKN2
Chemotherapy
Combined Modality Therapy
Complications and side effects
Cyclin-Dependent Kinase Inhibitor p15 - genetics
Cyclin-Dependent Kinase Inhibitor p16 - genetics
Cytogenetics
Dasatinib - administration & dosage
Deletion
Drug Resistance, Neoplasm - genetics
Female
Flow cytometry
Gene Deletion
Gene Expression Regulation, Leukemic
Genetic aspects
Health aspects
Hematology
Hematopoietic Stem Cell Transplantation - methods
Humans
Imatinib Mesylate - administration & dosage
In Situ Hybridization, Fluorescence
Influence
Kaplan-Meier Estimate
Kinases
Leukemia
Leukocytes
Male
Medical prognosis
Middle Aged
Oncology
Patients
Philadelphia chromosome
Polymerase chain reaction
Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy
Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics
Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy
Protein Kinase Inhibitors - administration & dosage
Protein Kinase Inhibitors - therapeutic use
Remission (Medicine)
Reverse Transcriptase Polymerase Chain Reaction
Stem cell transplantation
Transplantation, Homologous
Tyrosine
Tyrosine kinase inhibitors
Young Adult
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Summary:Frequency relapses are common in Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL) following tyrosine kinase inhibitors (TKIs). CDKN2A/B is believed to contribute to this chemotherapy resistance. To further investigate the association between CDKN2 status and TKI resistance, the prevalence of CDKN2 deletions and its correlation with a variety of clinical features was assessed in 135 Ph-positive ALL patients using interphase fluorescence in situ hybridization (I-FISH). Results showed that no difference occurred between patients with CDKN2 deletion (44/135) and wild-type patients in sex, age, and complete remission (CR) rate following induction chemotherapy combined with tyrosine kinase inhibitors (TKIs). However, CDKN2 deletion carriers demonstrated higher white blood cell (WBC) count, enhanced rates of hepatosplenomegaly (P = 0.006), and upregulation of CD20 expression (P = 0.001). Moreover, deletions of CDKN2 resulted in lower rates of complete molecular response (undetectable BCR/ABL), increased cumulative incidence of relapse, short overall survival (OS), and disease-free survival (DFS) time (P 
ISSN:1756-8722
1756-8722
DOI:10.1186/s13045-016-0270-5