The associations of Janus kinase-2 (JAK2) A830G polymorphism and the treatment outcomes in patients with acute myeloid leukemia

Abstract

The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway is active in both normal hematopoiesis and hematological malignancies. Moreover, Janus kinase-2 (JAK2) is the key hematopoietic kinase, and mutations together with single nucleotide polymorphisms (SNPs) of JAK2 have been thoroughly evaluated. In this study, we aimed to investigate whether the synonymous genetic polymorphism A830G in the JAK2 gene is associated with the treatment outcomes of Ara-C-based chemotherapy regimens in patients with acute myeloid leukemia (AML). A total of 152 patients with AML in a Chinese population were enrolled in our study. Peripheral blood samples drawn at the time of diagnosis were analyzed for the presence of JAK2 A830G by matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS). The results showed that frequencies of the AA genotype were higher in the group 40-60 years old, higher white blood cell (WBC) patient group, homoharringtonine and Ara-C (HA) regimen group, and good therapy response group, and patients with the GG genotype were significantly associated with a higher rate of early death. We conclude that the AA and GG genotypes of JAK2 A830G might be important markers for therapy outcomes of patients with AML in a Chinese population.

The prognostic impact of germline 46/1 haplotype of Janus kinase 2 in cytogenetically normal acute myeloid leukemia

“…[21][22][23] Single nucleotide polymorphisms of genes involved in hematopoietic signal-transduction were investigated less frequently. 24,25 In this study, we report an association of the JAK2 46/1 haplotype with disease characteristics and treatment out- 26,27 Retrieving haplotype information from the HapMap Project on rs12343867 and rs2230724 in a Chinese population revealed that the above polymorphisms are not in complete linkage (estimated haplotype frequencies of rs12343867/rs2230724: T/G: 57%, C/A: 23%, T/A: 18%, C/G: 2%, D': 0.892; P<0.000). 28 In Chinese AML patients, the AA genotype of rs2230724 was significantly associated with higher complete remission rate, and the GG genotype with early death.…”

JAK-1 rs2780895 C-Related Genotype and Allele but Not JAK-1 rs10789166, rs4916008, rs2780885, rs17127114, and rs3806277 Are Associated with Higher Susceptibility to Asthma

“…The JAK is the gatekeeper in the JAK-STAT pathway, which is a major suppressor of some cytokines during cell-signaling process. The JAK/STAT pathway is active in human malignancies (Zhong et al, 2010). Aberrant activation of the JAK/STAT pathway may predispose to malignancy because of deregulation of proliferation, differentiation, or apoptosis (Vaclavicek et al, 2007).…”

“…JAK gene polymorphisms were related with the susceptibility to disease activities for individual diseases. JAK mutations or SNPs are associated with leukemia (Zhong et al, 2010). The JAK SNP is part of a haplotype associated with enhanced susceptibility to myeloproliferative neoplasms.…”

“…The JAK SNP is part of a haplotype associated with enhanced susceptibility to myeloproliferative neoplasms. The JAK2 A830G might be an important marker for therapeutic outcomes of patients with acute myeloid leukemia (Zhong et al, 2010). JAK genetic variations are associated with the risk of Crohn's disease (Ferguson et al, 2010).…”

“…Some investigators demonstrated the correlation of JAK-2 or 3 and asthma or other disorders (Cools et al, 1999;Vaclavicek et al, 2007;Kudlacz et al, 2008;Sperati et al, 2009;Ferguson et al, 2010;Zhong et al, 2010). However, few investigators demonstrated the correlation of JAK-1 gene polymorphisms with asthma.…”