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MECOM Amplification on a Ring Chromosome 3 and a Marker, a Rare Cause of MECOM Overexpression in Acute Myeloid Leukemia

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MECOM Amplification on a Ring Chromosome 3 and a Marker, a Rare Cause of MECOM Overexpression in Acute Myeloid Leukemia Somato Publications Annals of Leukemia Research Research Article MECOM Amplification on a Ring Chromosome 3 and a Marker, a Rare Cause of MECOM Overexpression in Acute Myeloid Leukemia Karolien Beel1, Inge Vrelust2, Geneviève Ameye1, Barbara Dewaele1 and Lucienne Michaux1 1Center for Human Genetics, University Hospitals Leuven, Leuven, Belgium 2Department of Hematology, AZ Turnhout, Turnhout, Belgium *Address for Correspondence: Karolien Beel, Center for Human Genetics, University Hospitals Leuven, Leuven, Belgium, E-mail: [email protected] Received: 26 April 2019; Accepted: 18 May 2019; Published: 20 May 2019 Citation of this article: Beel, K., Vrelust, I., Ameye, G., Dewaele, B., Michaux, L. (2019) MECOM Amplification on a Ring Chromosome 3 and a Marker, a Rare Cause of MECOM Overexpression in Acute Myeloid Leukemia. Ann Leuk Res, 2(1): 005- 007. Copyright: © 2019 Beel K, et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. ABSTRACT Increased expression of MECOM is found in approximately 10% of patients with acute myeloid leukemia (AML) and is associated with chemoresistance and a poor prognosis. Chromosomal translocations involving chromosome band 3q26.2 explain only a minority of cases with MECOM overexpression. Here, we present a patient with intrachromosomal MECOM the complexity of mechanisms leading to MECOM overexpression in AML. amplification on a ring chromosome, demonstrating Our case underscores the need for FISH for the characterisation of chromosome 3 aberrations in AML. It also illustrates that overexpression of MECOM, irrespective of the underlying mechanism, is often accompanied by additional (secondary) karyotypic changes. Introduction are the most common [2]. In these cases, overexpression of MECOM results from the juxtaposition of a strong enhancing region next to MECOM is known as one of the most aggressive oncogenes the MECOM coding sequence. Some translocations can be detected since its discovery in 1988. Increased expression of MECOM with conventional chromosomal banding, but complex or cryptic is found in approximately 10% of patients with acute myeloid rearrangements require FISH for identification. Extrachromosomal leukemia (AML) and is associated with chemoresistance and a poor amplification of MECOM on double minutes has been described in prognosis. MECOM (MDS1 and EVI1 complex locus) was previously rare cases [3]. Epigenetic changes affecting MECOM have also been called EVI1 (ecotropic viral integration site 1), which is in fact a suggested. transcription variant of MECOM. The HUGO Gene Nomenclature Committee recently approved MECOM as the official gene symbol. Results The gene promotes cell proliferation, impairs cell differentiation and Here, we report a case with MECOM overexpression on a inhibits apoptosis, as induced by antileukemic drugs [1]. Increased ring chromosome. This male patient was diagnosed with acute expression of MECOM can result from chromosomal translocations megakaryoblastic leukemia (FAB AML M7) at the age of 73y. His involving the MECOM locus at chromosome band 3q26.2. At least history consisted of coronary artery disease and systemic lupus 12 recurrent chromosomal rearrangements involving MECOM erythematosus, for which steroids and cyclophosphamide had been have been described, accounting for 2% of AML cases, of which briefly administered in the past. At the time of diagnosis, he was rearrangement of MECOM with GATA2 [inv(3)(q21q26), t(3;3) mildly cognitively impaired and showed signs of malnutrition. Five (q21;q26)], ETV6 [t(3;12)(q26;p13)] and RUNX1 [t(3;21)(q26;q22)] months earlier, he had suffered from a cerebellar infarction and had Annals of Leukemia Research 05 Volume 2 Issue 1 - 1004 © 2019 Somato Publications. All rights reserved. Citation: Beel, K., Vrelust, I., Ameye, G., Dewaele, B., Michaux, L. (2019) MECOM Amplification on a Ring Chromosome 3 and a Marker, a Rare Cause of MECOM Overexpression in Acute Myeloid Leukemia. Ann Leuk Res, 2(1): 005-007. been resuscitated. He came to the Hematology department with a The bone marrow karyotype (Figure 1) was extremely complex, progressive pancytopenia with 2% peripheral blasts. Bone marrow and included e.g. additional material on one chromosome 3 aspirate showed acute megakaryocytic myeloid leukemia with 30.6% [add3] and monosomy 5. FISH analysis using Abbott Molecular blasts. The AML cells were positive in CD34, CD13, CD33, CD36, Laboratories (Chicago, IL USA) and Metasystems (Altlußheim, weakly positive in CD117, HLADR, CD71, CD105, CD35, partially Germany) probes was subsequently performed. Using a dual colour positive in CD11b and negative in CD10, CD16, cytCD79a, cytCD3, dual fusion MECOM/RPN1 probe, one normal chromosome 3 and CD3, cytMPO, CD14, CD15 and CD64.The patient was treated with one ring chromosome, displaying amplification of MECOM were decitabine for one cycle and died at home, within one month after observed in 43% of interphase nuclei and 2/5 metaphases (Figure 2). diagnosis. Additionally, a marker with 1 MECOM signal was seen and add(3) Figure 1: Original Ultrasound: non-encapsulating irregular hypoechoic masses and soft tissue edema categorized as a BIRADS 4. A B C Figure 2: A=B=C A= 63159644.068 with Vysis RPN1/MECOM DF FISH Probe Kit (CE) (RPN1/3q21.3 SpectrumGreen, MECOM/3q26.2 SpectrumOrange) B= 63159644.088 with Metasystems XCP 3 Orange (painting of chromosome 3) C= 63159644.106 with Metasystems XCP 19 Orange (painting of chromosome 19) and XCE 3 Green (centromere 3) vFull arrow = ring Arrow with line = mar2 Empty arrow = normal chromosome 3 Empty triangle = der(3)t(3;?)(q11;?) Full triangle = der(?)t(19;?) Annals of Leukemia Research 06 Volume 2 Issue 1 - 1004 © 2019 Somato Publications. All rights reserved. Citation: Beel, K., Vrelust, I., Ameye, G., Dewaele, B., Michaux, L. (2019) MECOM Amplification on a Ring Chromosome 3 and a Marker, a Rare Cause of MECOM Overexpression in Acute Myeloid Leukemia. Ann Leuk Res, 2(1): 005-007. displayed neither MECOM nor GATA2. Using a whole chromosome banding and require FISH with the dual colour MECOM probe as a paint, no other material derived from chromosome 3 was detected supplement for detection of MECOM overexpression and for therapy on the marker chromosome, whereas part of the add(3) and almost monitoring. all the ring were painted. In addition, using a centromeric probe for chromosome 3, no signal was observed on the ring. References 1. Lugthart, S., van Drunen, E., van Norden, Y., van Hoven, A., Erpelinck, Discussion CA., Valk, PJ., et al. (2008) High EVI1 levels predict adverse outcome in acute myeloid leukemia: prevalence of EVI1 overexpression and This case illustrates a new rare and rather complex presentation chromosome 3q26 abnormalities underestimated. Blood, 111(8): of intrachromosomal MECOM overexpression. Our case supports 4329-4337. the finding that overexpression of MECOM, irrespective of the 2. Hinai, AA.,Valk, PJ. (2016) Aberrant EVI1 expression in acute myeloid underlying mechanism, is often accompanied by additional leukaemia. Br J Haematol, 172(6): 870-878. karyotypic changes, in this case a deletion of chromosome 5q, but sometimes also monosomy 7 (in 66%). These additional changes 3. Volkert, S., Schnittger, S., Zenger, M., Kern, W., Haferlach, T., Haferlach, EVI1 on cytogenetically cryptic double appear to worsen the already poor prognosis. The case particularly minutes as new mechanism for increased expression of EVI1. Cancer underscores that MECOM overexpression can be observed without Genet,C. (2014) 207(3): Amplification 103-108. of a detectable 3q26 chromosomal rearrangement (between 6 and 11% 4. Wieser, R. (2007) The oncogene and developmental regulator EVI1: of patients with AML) [4]. Hence, complex or cryptic chromosome expression, biochemical properties, and biological functions. Gene, 3q26.2 rearrangements can be missed by conventional chromosomal 396(2): 346-357. Annals of Leukemia Research 07 Volume 2 Issue 1 - 1004 © 2019 Somato Publications. All rights reserved..
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