Array comparative genomic hybridization analysis of adult acute leukemia patients

Yasar, Duygu; Karadoğan, İhsan; Alanoğlu, Güçhan; Akkaya, Bahar; Lülecı, Güven; Salim, Ozan; Timurağaoğlu, Ayşen; Toruner, Gokce; Berker-Karaüzüm, Sibel

doi:10.1016/j.cancergencyto.2009.11.018

Cited by 20 publications

(22 citation statements)

References 19 publications

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“…CBL and Egr2 were selected as putative miR-150 targets as they are known to be deregulated in leukemia and contain predicted miR-150-binding sites in their 3 0 -UTR (28)(29)(30)(31)(32)(33). We confirmed downregulation of these genes by qRT-PCR as shown in Fig.…”

Section: Restoration Of Mir-150 In Mll-af9 Cells Impairs the Colony Isupporting

confidence: 54%

miR-150 Blocks MLL-AF9–Associated Leukemia through Oncogene Repression

Bousquet

Zhuang

et al. 2013

Molecular Cancer Research

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The microRNA miR-150, a critical regulator of hematopoiesis, is downregulated in mixed-lineage leukemia (MLL). In this study, miR-150 acts as a potent leukemic tumor suppressor by blocking the oncogenic properties of leukemic cells. By using MLL-AF9-transformed cells, we demonstrate that ectopic expression of miR-150 inhibits blast colony formation, cell growth, and increases apoptosis in vitro. More importantly, ectopic expression of miR-150 in MLL-AF9-transformed cells completely blocked the development of myeloid leukemia in transplanted mice. Furthermore, gene expression profiling revealed that miR-150 altered the expression levels of more than 30 "stem cell signature" genes and many others that are involved in critical cancer pathways. In addition to the known miR-150 target Myb, we also identified Cbl and Egr2 as bona fide targets and shRNA-mediated suppression of these genes recapitulated the pro-apoptotic effects observed in leukemic cells with miR-150 ectopic expression.In conclusion, we demonstrate that miR-150 is a potent leukemic tumor suppressor that regulates multiple oncogenes.Implications: These data establish new, key players for the development of therapeutic strategies to treat MLL-AF9-related leukemia. Mol Cancer Res; 11(8); 912-22. Ó2013 AACR.

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Section: Restoration Of Mir-150 In Mll-af9 Cells Impairs the Colony Isupporting

confidence: 54%

miR-150 Blocks MLL-AF9–Associated Leukemia through Oncogene Repression

Bousquet

Zhuang

et al. 2013

Molecular Cancer Research

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“…Rearrangements of the RB1 gene in pre-B ALL were found in 38% of pediatric patients [23]. Other authors have also found RB1 gene deletion exclusively in B-ALL, in 16% of children and 11% of adults, respectively [17,18]. Our findings did not support this observation because RB1 gene deletions were present in both T and B-lineage ALL.…”

Section: F -Female; M -Male; Ir -Intermediate Risk; Sr -Standard Riskcontrasting

confidence: 57%

“…According to various authors these alterations are present in 2-38% of patients [15][16][17]. Discrepancies in findings of different authors may result from various methods employed, distinct leukemia types and differences in ethnicity of studied patients [4,5,18,19]. The percentage of cells showing deletions has not been evaluated in individual ALL patients.…”

Section: Discussionmentioning

confidence: 99%

Allelic loss of selected tumor suppressor genes in acute lymphoblastic leukemia in children

Studniak¹,

Maloney²,

Ociepa³

et al. 2013

pjp

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Defect in function of tumor suppressor genes may lead to initiation/progression of leukemias. RB1, CDKN2A and TP53 gene alterations are found in acute lymphoblastic leukemia (ALL) in children. Data showing a contribution of these alterations to the pathomechanism of leukemias are contradictory and their impact on a disease course still remains undefined. The main aim of the study was to identify and the characterize of RB1, CDKN2A and TP53 allele loss in ALL children patients at diagnosis. 46 children with de novo ALL were examined. Fluorescent in situ hybridization was performed on bone marrow smear preparations. We demonstrated that at least one of three investigated deletions occurred statistically more frequently in T-lineage leukemia patients (p = 0.044); this was the most frequent in respect to RB1 gene (p = 0.054). Additionally, at least one of the examined deletions was observed statistically more frequently in patients with WBC above 20 000/µl (p = 0.043), this was the most frequent for CDKN2A gene (p = 0.066). Presented results seem to give an evidence that deletions of RB1 and CDKN2A genes may contribute to the development of hyperleukocytic type of T-lineage ALL in children, nevertheless this observation needs further investigations.

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“…aCGH overcomes the limitations of conventional cytogenetic analysis by allowing for a more in depth assessment of the genome in AML patients. These findings will likely better characterize the intermediate- and poor-risk categories of AML and will facilitate detection of additional abnormalities in favorable-risk AML patients that may further aid in risk stratification, as a subset of patients in the favorable-risk group respond well to therapy [5,13,14,16,21,22]. …”

Section: Discussionmentioning

confidence: 99%

“…In cases assessed by conventional cytogenetic analysis of FISH, aCGH can show additional genomic imbalances emphasizing the advantages of a whole-genome approach [1,4,5,11–13]. Despite the great potential of aCGH to assess cases of AML, relatively few studies of AML patients assessed by aCGH have been published [14–16]. …”

Section: Introductionmentioning

confidence: 99%

Identification of clinically important chromosomal aberrations in acute myeloid leukemia by array-based comparative genomic hybridization

Mehrotra

Luthra²,

Ravandi

et al. 2014

Leukemia & Lymphoma

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Array-based comparative genomic hybridization (aCGH) chromosomal analysis facilitates rapid detection of cytogenetic abnormalities previously undetectable by conventional cytogenetics. In this study, we analyze 48 uniformly treated acute myeloid leukemia (AML) patients by 44K aCGH and correlated the findings with clinical outcome. aCGH identified previously undetected aberrations, as small as 5 kb, of currently unknown significance. The 36.7 Mb minimally deleted region on chromosome 5 lies between 5q14.3 to 5q33.3 contains 634 genes and 15 microRNAs whereas loss of chromosome 17 spans 3,194 kb involves 342 genes and 12 microRNAs. Loss of 155 kilobase (kb) region on 5q33.3 (p<0.05) is associated with achievement of complete remission. In contrast, loss of 17p11.2-q11.1 was associated with lower CR rate and poorer overall survival (Kaplan-Meier analysis, p<0.0096). aCGH detected loss of 17p in 12/48 patients as compared to 9/48 by conventional karyotyping. In conclusion, aCGH analysis adds to the prognostic stratification of AML patients.

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Array comparative genomic hybridization analysis of adult acute leukemia patients

Cited by 20 publications

References 19 publications

miR-150 Blocks MLL-AF9–Associated Leukemia through Oncogene Repression

miR-150 Blocks MLL-AF9–Associated Leukemia through Oncogene Repression

Allelic loss of selected tumor suppressor genes in acute lymphoblastic leukemia in children

Identification of clinically important chromosomal aberrations in acute myeloid leukemia by array-based comparative genomic hybridization

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