KIR2DL5B genotype predicts outcomes in CML patients treated with response-directed sequential imatinib/nilotinib strategy.
Killer immunoglobulin-like receptors (KIRs) on natural killer (NK) cells have been shown to predict for response in chronic phase-chronic myeloid leukemia (CP-CML) patients treated with tyrosine kinase inhibitors. We performed KIR genotyping in 148 newly diagnosed CP-CML patients treated with a novel sequential imatinib/nilotinib strategy aimed at achievement of optimal molecular responses at defined time points. We found the presence of KIR2DL5B to be associated with inferior transformation-free survival and event-free survival and an independent predictor of inferior major molecular response (BCR-ABL1 ≤0.1%) and molecular response 4.5 (BCR-ABL1 ≤0.0032%). This suggests a critical early role for NK cells in facilitating response to imatinib that cannot be overcome by subsequent intensification of therapy. KIR genotyping may add valuable prognostic information to future baseline predictive scoring systems in CP-CML patients and facilitate optimal frontline treatment selection.
Department of Genetics and Molecular Pathology, Centre for Cancer Biology, and Department of Haematology, SA Pathology, Adelaide, SA, Australia; School of Medicine and.
David T
http://orcid.org/0000-0002-1505-2001
DT
Yeung
Department of Haematology, SA Pathology, Adelaide, SA, Australia; School of Medicine and.
Carine
C
Tang
Department of Haematology, SA Pathology, Adelaide, SA, Australia;
Ljiljana
L
Vidovic
School of Medicine and School of Paediatrics, University of Adelaide, Adelaide, SA, Australia; Cancer Theme, South Australia Health and Medical Research Institute, Adelaide, SA, Australia;
Deborah L
DL
White
Department of Genetics and Molecular Pathology, Centre for Cancer Biology, and School of Pharmacy and Medical Science, University of South Australia, Adelaide, SA, Australia; and School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA, Australia.
Susan
S
Branford
Department of Haematology, SA Pathology, Adelaide, SA, Australia; School of Medicine and Cancer Theme, South Australia Health and Medical Research Institute, Adelaide, SA, Australia;
Timothy P
TP
Hughes
Department of Haematology, SA Pathology, Adelaide, SA, Australia; School of Medicine and.
Agnes S
AS
Yong
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005838:Genotype; D006801:Humans; D000068877:Imatinib Mesylate / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D011743:Pyrimidines / Q000008:administration & dosage; D054346:Receptors, KIR2DL5 / Q000235:genetics*; D016896:Treatment Outcome
C515081:KIR2DL5B protein, human; D011743:Pyrimidines; D054346:Receptors, KIR2DL5; D000068877:Imatinib Mesylate; C498826:nilotinib