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Significance of spatial organization of chromosomes in the progression of acute myeloid leukemia

X. Tian,Yanfang Wang,Dieyan Chen,X. Ke,Wanyun Ma

Published 2017 in Chinese journal of cancer

ABSTRACT

© The Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Dear editor Leukemia ranks as one of the ten most fatal cancers [1]. The mortality and incidence of this disease are associated with multiple factors, including environmental factors, sex, and age. Distinct genetic and chromosomal aberrations differentially affect the phenotype and prognosis of individuals with leukemia [2, 3]. The t(8;21)(q22;q22) translocation, which is observed in patients with acute myeloid leukemia with maturation (AML-M2, according to the French–American–British classification system), is characterized by the fusion of AML1 (acute myeloid leukemia factor 1, also referred to as RUNX1 [runt-related transcription factor 1]) on chromosome 21 and ETO (eight-twenty-one, also referred to as RUNX1T1 [runtrelated transcription factor 1, translocated to 1]) on chromosome 8. Although the t(8;21)(q22;q22) translocation is associated with a favorable prognosis, relapse remains the primary cause of treatment failure [4]. Real-time fluorescent quantitative polymerase chain reaction (RQ-PCR) is a powerful tool for monitoring the presence of residual disease and planning treatment strategies [5, 6]; however, this technique is not 100% accurate [7]. The three-dimensional organization of chromosomes might be a valuable prognostic marker of the risk of relapse in patients with t(8;21)(q22;q22)-positive AML [8]. To further study the utility of this approach, we evaluated bone marrow (BM) samples from a patient with t(8;21)(q22;q22)-positive AML-M2 before and after hematopoietic stem cell transplantation (HSCT) using three-dimensional fluorescence in situ hybridization (3D-FISH) and confocal laser scanning microscopy to delineate and analyze the spatial organization of the target chromosomes. AML1-ETO fusion transcripts detected by RQ-PCR were also discussed in this article. The 35-year-old male patient was diagnosed with t(8;21)(q22;q22)-positive AML-M2 in January 2013 in Peking University Third Hospital. He was treated with induction chemotherapy and achieved the first complete remission (CR1) in March 2013. However, he deteriorated since November 2014 and relapsed in January 2015. The patient received induction chemotherapy again and achieved the second complete remission (CR2) in March 2015. Then he underwent HSCT in June 2015 and relapsed again in November 2015. Using aspiration, BM specimens (4 mL each) were extracted from the patient when he achieved CR2 (CR2 sample), 2 months after HSCT (post-HSCT sample), 3 months after HSCT (follow-up 1 sample), and 2 months after the first follow-up (follow-up 2 sample). The fifth BM sample (relapse) was extracted 2 weeks after the second follow-up, when the patient relapsed. Mononuclear cells were isolated from the BM specimens using density gradient centrifugation, and total RNA was extracted using TRIzol Reagent (Invitrogen, Carlsbad, CA, USA). Complementary DNA (cDNA) was synthesized using the ProFlex PCR System (Applied Biosystems, Foster City, CA, USA), and RQ-PCR experiments were conducted to detect the AML1-ETO fusion transcripts using the 7500 Real-time PCR System (Applied Biosystems) and TaqMan technology. Abelson (ABL) was used as the reference gene. Representative RQ-PCR curves for the relapse sample were drawn using the OriginPro 8 software (OriginLab Corporation, Northampton, MA, USA) (Fig. 1). The threshold cycle was defined as the cycle number at which the fluorescence surpassed the threshold value. The threshold value was defined as a value greater than the baseline value but sufficiently low enough to lie within Open Access Chinese Journal of Cancer

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