Spectrum of mitochondrial genome instability and implication of mitochondrial haplogroups in Korean patients with acute myeloid leukemia
Blood Research 2018³â 53±Ç 3È£ p.240 ~ p.249
±èÇý¶õ(Kim Hye-Ran) - Dongshin University College of Korean Medicine
°¹Î±¸(Kang Min-Gu) - Gwangyang Sarang General Hospital Department of Laboratory Medicine
ÀÌ¿µÀº(Lee Young-Eun) - Chonnam National University Medical School Chonnam National University Hwasun Hospital Department of Laboratory Medicine
³ªº¸¶÷(Na Bo-Ram) - Chonnam National University Medical School Chonnam National University Hwasun Hospital Department of Laboratory Medicine
(Noh Min-Seo) - Chonnam National University Medical School Chonnam National University Hwasun Hospital Department of Laboratory Medicine
¾ç½ÂÇö(Yang Seung-Hyun) - Chonnam National University Medical School Chonnam National University Hwasun Hospital Department of Laboratory Medicine
½ÅÁ¾Èñ(Shin Jong-Hee) - Chonnam National University Medical School Chonnam National University Hwasun Hospital Department of Laboratory Medicine
(Shin Myun-Geun) - Chonnam National University Medical School Chonnam National University Hwasun Hospital Department of Laboratory Medicine
Abstract
Background: Mitochondrial DNA (mtDNA) mutations may regulate the progression and chemosensitivity of leukemia. Few studies regarding mitochondrial aberrations and haplogroups in acute myeloid leukemia (AML) and their clinical impacts have been reported. Therefore, we focused on the mtDNA length heteroplasmies minisatellite instability (MSI), copy number alterations, and distribution of mitochondrial haplogroups in Korean patients with AML.
Methods: This study investigated 74 adult patients with AML and 70 controls to evaluate mtDNA sequence alterations, MSI, mtDNA copy number, haplogroups, and their clinical implications. The hypervariable (HV) control regions (HV1 and HV2), tRNAleu1gene, and cytochrome b gene of mtDNA were analyzed. Two mtDNA minisatellite markers, 16189 poly-C (16184CCCCCTCCCC16193, 5CT4C) and 303 poly-C (303CCCCCCCTCCCCC315, 7CT5C), were used to examine the mtDNA MSI.
Results: In AML, most mtDNA sequence variants were single nucleotide substitutions, but there were no significant differences compared to those in controls. The number of mtMSI patterns increased in AML. The mean mtDNA copy number of AML patients increased approximately 9-fold compared to that of controls (P<0.0001). Haplogroup D4 was found in AML with a higher frequency compared to that in controls (31.0% vs. 15.7%, P=0.046). None of the aforementioned factors showed significant impacts on the outcomes.
Conclusion: AML cells disclosed more heterogeneous patterns with the mtMSI markers and had increased mtDNA copy numbers. These findings implicate mitochondrial genome instability in primary AML cells. Therefore, mtDNA haplogroup D4 might be associated with AML risk among Koreans.
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AML, Mitochondrial genome, Instability, Haplogroup, Outcome
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AML cells revealed more heterogeneous patterns in mtMSI markers and had increased mtDNA copy numbers.