ABSTRACT
Objective:
To explore the characteristics of BCR-ABL1
kinase domain
mutations in
imatinib-resistant
chronic myelogenous leukemia (CML) and
Philadelphia chromosome-positive
acute lymphoblastic leukemia (
Ph + ALL)
patients from Northeast
China and their impact on
prognosis.
Methods:
The clinical data of 252 CML
patients and 49
Ph + ALL
patients who were admitted to the First
Hospital of Jilin
University from January 2013 to October 2018 were retrospectively analyzed. The samples of
bone marrow or peripheral
blood were collected from
patients when
imatinib treatment was not effective.
Nested polymerase chain reaction (
PCR) was used to amplify the BCR-ABL1
kinase domain, and Sequencing
Analysis v5.4
software was used to analyze the
mutation of BCR-ABL1
kinase domain.
Patients were followed up for 6-48 months, and the
survival analysis was performed.
Results:
Among 252 CML
patients, the
mutations in ABL1
kinase domain were found in 57
patients (22.6%), including 25
patients in the chronic phase, 21
patients in the accelerated phase and 11
patients in the
blast crisis; 50
patients had 20 types of single
point mutation, and the most common
mutation types were E255K (16.0%, 8/50), T315I (14.0%, 7/50), M244V (8.0%, 4/50) and G250E (8.0%, 4/50), which were all concentrated in the
P-loop and C-helix domains; 7
patients had double
mutations;
patients with multiple
mutations had the worst
prognosis, with a median overall
survival (OS)
time of 3.2 months. Among 49
Ph + ALL
patients, 17 cases (34.7%) were positive for
mutations in the BCR-ABL1
kinase domain, 14
patients had 12 types of single
point mutation, and 3
patients had multiple
mutations; the median OS
time of
patients with multiple
mutations,
mutations located in the
P-loop and C-helix domains and
mutations located in the other domains was 2.0, 8.0 and 18.0 months, and the difference in OS among the three groups was statistically significant ( P < 0.01).
Conclusions:
Among the
imatinib-resistant CML and
Ph + ALL
patients from Northeast
China,
point mutations in the
P-loop and C-helix domains are most commonly found. Multiple
mutations,
mutations in the
P-loop and C-helix domains are related to the poor
prognosis of the
patients.