Polymorphisms in XRCC5, XRCC6, XRCC7 genes are involved in DNA double-strand breaks(DSBs) repair associated with the risk of acute myeloid leukemia(AML) in Chinese population

Abstract Abstract 4858 Objectives: In the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway signaling pathway, the STAT3 is one of the most prominent predictable factors for cancer and leukemia. STAT3 activation might promote cellular transformation and therefore have an important role in human tumors. This study was aimed to investigate the relationship between the STAT3 polymorphisms and the treatment responses of AML in the Chinese population. Methods: We tested three single nucleotide polymorphisms (SNPs) with 130 Acute Myeloid Leukemia (AML) patients. Genomic DNA was isolated from peripheral blood and assayed by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF). Results: The results showed there were strong relationship between unfavorable cytogenetic, partial remission (even no remission) and the frequencies of GG genotype in rs9909659 (P=0.01 and 0.03) and the patients less than 45 years old was significant association with GA/AA genotype (P=0.01). But associations were not confirmed about event-free survival and leukemia-free survival in the Chinese population studied. Conclusions: It is clear that the AML patients with GG genotype in rs9909659 are not sensitive to standard chemotherapy method Disclosures: No relevant conflicts of interest to declare.

Download Full-text

NBS1 rs1805794G>C polymorphism is associated with decreased risk of acute myeloid leukemia in a Chinese population

Molecular Biology Reports ◽

10.1007/s11033-012-2451-9 ◽

2013 ◽

Vol 40 (5) ◽

pp. 3749-3756 ◽

Cited By ~ 7

Author(s):

Na Li ◽

Yanzhe Xu ◽

Jian Zheng ◽

Lan Jiang ◽

Yonghe You ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Chinese Population ◽

Myeloid Leukemia ◽

Acute Myeloid

Download Full-text

Sensitivity of fresh acute myeloid leukemia cells to etoposide: relationship with cell growth characteristics and DNA single-strand breaks

Blood ◽

10.1182/blood.v80.5.1307.bloodjournal8051307 ◽

1992 ◽

Vol 80 (5) ◽

pp. 1307-1315

Author(s):

M Chiron ◽

C Demur ◽

V Pierson ◽

JP Jaffrezou ◽

C Muller ◽

...

Keyword(s):

Dna Repair ◽

Acute Myeloid Leukemia ◽

Cell Growth ◽

Cell Population ◽

Myeloid Leukemia ◽

Growth Characteristics ◽

Single Strand ◽

Strand Breaks ◽

Single Strand Breaks ◽

Acute Myeloid

In this study, we evaluated the individual in vitro sensitivity of fresh acute myeloid leukemia (AML) cells to VP-16, and attempted to correlate VP-16 cytotoxicity with AML cell growth characteristics and drug-induced DNA single-strand breaks (SSB). Primary (PE1) colony inhibition assays allowed us to characterize two distinct groups of AML: group I (patients 1 through 6), which displayed sensitivity to VP- 16 similar to that of normal CFU-GM (IC90 of 20.52 +/- 2.44 micrograms/mL v 20.48 +/- 2.23 micrograms/mL after 1 hour drug exposure, respectively); and group II (patients 7 through 11), which was more sensitive to VP-16 (IC90 of 7.26 +/- 2.93 micrograms/mL, P = .004). Subsequently, groups I and II were termed normosensitive and hypersensitive, respectively. This objective VP-16 sensitivity classification, as determined by PE1, remained unaltered when assessed by secondary (PE2) colony inhibition assay (evaluating the self-renewal fraction of AML progenitors), or by cytofluorometric viability assay (evaluating the ultimately differentiated blast cell population). These findings would suggest that individual sensitivity to VP-16 of a particular cell population is maintained throughout CFU-AML differentiation. Finally, we report that sensitivity of AML cells to VP- 16 did not correlate either with cell growth characteristics or with SSB generation. Indeed, AML cell sensitivity to VP-16 appeared more closely related to DNA repair kinetics after drug removal, ie, hypersensitivity being essentially characterized by a prolonged retention of SSB during the posttreatment period. Interestingly, the established HL-60 cell line, which presented greater sensitivity to VP- 16 cytotoxicity than KG1, HEL, and K562, was also found to exhibit delayed DNA SSB repair kinetics, as compared with the other AML cell lines. These results suggest that hypersensitivity to VP-16 of some AML cells may be related to a deficient DNA-repair mechanism.

Download Full-text