Expression and clinical significance of relative telomere length and telomerase activity in CD34+ CD38+ acute myeloid leukemia

Abstract

Objective To discuss the clinical and guiding signification of relative telomere length and telomerase activity in diagnosis, prognosis and treatment of CD34+ CD38+ acute myeloid leukemia (AML). Methods From April to July 2015, a total of 20 cases of newly diagnosed CD34+ CD38+ AML patients who were hospitalized in Department of Hematology, Xiangya Hospital, Central South University were selected randomly as study subjects and enrolled in study group (n=20). And 10 cases of participants who were conducted bone marrow puncture due to suspected blood system malignant diseases were selected as control group, randomly (n=10). Relative quantitative PCR was conducted to detect relative telomere length of participants′ bone marrow specimens in two groups, and telomere repeat sequence amplification method (TRAP)-argentation and absolute quantitative PCR were conducted to detect telomerase activity; rate of complete remission (CR) after chemotherapy was collected in study group. MRD was obtained by flow cytometry. Relative telomere length, telomerase activity of two groups, relationship between relative telomere lengths, telomerase activity and clinical data, curative effect, MRD and prognosis of study group were analyzed retrospectively and compared statistically. The study protocol was approved by the Ethical Review Board of Investigation in Human at Xiangya Hospital, Central South University. Informed consent was obtained from all participants. There were no significant differences in average age and constituent ratio of gender between two groups (P>0.05). Results ① As TRAP-argentation showed, the telomerase activity of CD34+ CD38+ AML patient in study group was higher than that of control group. Relative quantitative PCR of telomere and absolute quantitative PCR of telomerase showed, relative telomere length of study group was 1.72±0.42, and significantly shorter than that of control group which was 4.68±1.89 (t=-6.906, P=0.002 0). Telomerase activity of study group was (405 242.01±357 412.39) copies/μL, and significantly higher than that of control group which was (17 956.53±6 952.03) copies/μL (t=3.357, P=0.002). There was a negative correlation between relative telomere length and telomerase activity in study group (r=-0.508, P 0.05). Compared with CD7- patients and patients with hemoglobin (Hb) level≤50 g/L, relative telomere length of CD7+ patients and patients with Hb level within (>50-120) g/L were significantly shorter(t=-2.217, -3.011; P=0.040, 0.008), and their telomerase activity were significantly higher (t=3.253, 2.255; P=0.010, 0.037). Compared with patients with immature cells ratio>50%, white blood cell count>50×109/L, relative telomere length and telomerase activity of patients with immature cells ratio≤50%, white blood cell count≤50×109/L were significantly longer (t=4.218, 2.637; P=0.001, 0.018), their telomerase activity were significantly lower (t=-3.052, -3.281; P=0.009, 0.008). ③ In study group, relative telomere length of CD34+ CD38+ AML patients who achieved CR was 1.95±0.19, and significantly longer than that of patients who didn′t achieve CR, which was 1.28±0.38 (t=5.336, P 1.95, MRD of 1 case was positive, and 5 cases were negative. Among 7 cases with telomerase activity≤197 670.43 copies/μL, MRD of 1 case was positive, and 6 cases were negative. Among the 6 cases with telomerase activity>197 670.43 copies/μL, MRD of 5 cases were positive, 1 case was negative. From August 2015 and March 2016, follow-up of 5 patients who achieved CR showed, relative telomere length and telomerase activity of the 3 cases with long-term in CR were similar to these of control group. Relative telomere length shortened, and telomerase activity elevated again in 2 cases with recurrence. Conclusions The relative telomere length and telomerase activity can be used as one of the diagnostic, prognostic and recurrent criteria of CD34+ CD38+ AML, and provide some theoretical basis for the determination of treatment options. Key words: Leukemia, myeloid, acute; Telomere; Telomerase; Polymerase chain reaction