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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The presence of cytogenetic aberrations on mesenchymal stem cells (MSC) from myelodysplastic syndrome (MDS) patients is controversial. The aim of the study is to characterize bone marrow (BM) derived MSC from patients with MDS using: kinetic studies, immunophenotyping, fluorescent in situ hybridization (FISH) and genetic changes by array-based comparative genomic hybridization (array-CGH). In all 36 cases of untreated MDS were studied. MDS-MSC achieved confluence at a significantly slower rate than donor-MSC, and the antigenic expression of CD105 and CD104 was lower. Array-CGH studies showed DNA genomic changes that were proved not to be somatic. These results were confirmed by FISH. To confirm that genomic changes were also present in freshly obtained MSCs they were enriched by sorting BM cells with the following phenotype: CD45(-)/CD73(++)/CD34(-)/CD271(++). They also showed genomic changes that were confirmed by FISH. To analyze the relationship of these aberrations with clinical-biological data an unsupervised hierarchical cluster analysis was performed, two clusters were identified: the first one included the 5q- syndrome patients, whereas the other incorporated other MDS. Our results show, for the first time that MSC from MDS display genomic aberrations, assessed by array-CGH and FISH, some of them specially linked to a particular MDS subtype, the 5q- syndrome.
Leukemia 2009 Apr
PMID:Both expanded and uncultured mesenchymal stem cells from MDS patients are genomically abnormal, showing a specific genetic profile for the 5q- syndrome. 1915 77

AML/MDS patients carrying 11q amplifications involving the mixed lineage leukemia gene (MLL) locus are characterized by a complex aberrant karyotype (CAK) frequently including deletions within 5q, 17p, and 7q, older age and fast progression of the disease with extremely poor prognosis. MLL has been shown to be overexpressed in cases with 11q amplification. However, in most of the cases, the amplified region is not restricted to the MLL locus. In this study, we investigated 19 patients with AML/MDS and MLL gain/amplification. By means of array CGH performed in 12 patients, we were able to delineate the minimal deleted regions within 5q and 17p and identified three independent regions 11q/I-III that were amplified in all cases. Gene expression profiles established in 15 cases were used to identify candidate genes within these regions. Notably, analysis of our data suggests a correlation of loss of 5q and 17p and expression of genes present in 11q23-25. Furthermore, we demonstrate that the gene expression signature can be used to discriminate AML/MDS with MLL amplification from several other types of AML.
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PMID:AML/MDS with 11q/MLL amplification show characteristic gene expression signature and interplay of DNA copy number changes. 1930 56

It is an open question whether in multiple myeloma (MM) bone marrow stromal cells contain genomic alterations, which may contribute to the pathogenesis of the disease. We conducted an array-based comparative genomic hybridization (array-CGH) analysis to compare the extent of unbalanced genomic alterations in mesenchymal stem cells from 21 myeloma patients (MM-MSCs) and 12 normal donors (ND-MSCs) after in vitro culture expansion. Whereas ND-MSCs were devoid of genomic imbalances, several non-recurrent chromosomal gains and losses (>1 Mb size) were detected in MM-MSCs. Using real-time reverse transcription PCR, we found correlative deregulated expression for five genes encoded in regions for which genomic imbalances were detected using array-CGH. In addition, only MM-MSCs showed a specific pattern of 'hot-spot' regions with discrete (<1 Mb) genomic alterations, some of which were confirmed using fluorescence in situ hybridization (FISH). Within MM-MSC samples, unsupervised cluster analysis did not correlate with particular clinicobiological features of MM patients. We also explored whether cytogenetic abnormalities present in myelomatous plasma cells (PCs) were shared by matching MSCs from the same patients using FISH. All MM-MSCs were cytogenetically normal for the tested genomic alterations. Therefore we cannot support a common progenitor for myeloma PCs and MSCs.
Leukemia 2009 Aug
PMID:Mesenchymal stem cells from multiple myeloma patients display distinct genomic profile as compared with those from normal donors. 1935 1

Little is known about the cytogenetic features and molecular mechanisms behind hairy cell leukaemia (HCL), despite the advances in diagnosis and treatment. Therefore, we used high-resolution genome-wide array-based comparative genomic hybridisation (array-CGH) and multiplex ligation-dependent probe amplification (MLPA) to characterise copy number alterations (CNAs) in DNA from 13 cases of HCL. We also summarise CNAs and cytogenetic features in 109 HCL cases comprising our 13 cases and 96 cases from the literature. Genomic array-CGH revealed imbalances in two out of 13 cases in addition to previously described copy number variants (CNVs) found in healthy individuals. In one case, a 700 kb deletion of 20q11.22 was detected encompassing ten characterised genes, among them the TP53INP2, DNCL2A and ITCH genes. In the second case, trisomy 5, and a deletion of 5p15.2 encompassing a non-characterised gene AY328033 was found. Altogether only 20/81 (25%) of all cases studied by CGH or gene dose array revealed CNAs. The most common recurrent deletions and breakpoints were 14q22-32 (33%), 6q25 (16%), 2p12 (10%), 22q11 (10%), 17p11-13 (10%), 7q32-36 (9%), 18q11-13 (7%), 1q32-44 (6%), 8p22-23 (6%) and 7q11 (6%). Trisomy 5 occurred in 15%. In addition, several other recurrent breakpoints were identified. Although a number of genomic imbalances were identified in the HCL samples, the genome appeared remarkably stable.
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PMID:Characterisation of hairy cell leukaemia by tiling resolution array-based comparative genome hybridisation: a series of 13 cases and review of the literature. 1968 64

The t(8;21) Acute Myeloid Leukaemia (AML) Kasumi-1 cell line with N822K KIT mutation, is a model system for leukemogenesis. As AML initiating cells reside in the CD34(+)CD38(-) fraction, we addressed the refined cytogenomic characterization and miRNA expression of Kasumi-1 cell line and its FACS-sorted subpopulations focussing on this compartment. By conventional cytogenetics, Spectral-Karyotyping and array-CGH the cytogenomic profile of Kasumi-1 cells evidenced only subtle regions differentially represented in CD34(+)CD38(-) cells. Expression profiling by a miRNA platform showed a set of miRNA differentially expressed in paired subpopulations and the signature of miR-584 and miR-182 upregulation in the CD34(+)CD38(-) fraction.
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PMID:Differential cytogenomics and miRNA signature of the Acute Myeloid Leukaemia Kasumi-1 cell line CD34+38- compartment. 2022 11

Therapy-related acute leukemia (t-AML), is a severe complication of cytotoxic therapy used for primary cancer treatment. The outcome of these patients is poor, compared to people who develop de novo acute leukemia (p-AML). Cytogenetic abnormalities in t-AML are similar to those found in p-AML but present more frequent unfavorable karyotypes depending on the inducting agent. Losses of chromosome 5 or 7 are observed after alkylating agents while balanced translocations are found after topoisomerase II inhibitors. This study compared t-AML to p-AML using high resolution array CGH in order to find copy number abnormalities (CNA) at a higher resolution than conventional cytogenetics. More CNAs were observed in 30 t-AML than in 36 p-AML: 104 CNAs were observed with 63 losses and 41 gains (mean number 3.46 per case) in t-AML, while in p-AML, 69 CNAs were observed with 32 losses and 37 gains (mean number of 1.9 per case). In primary leukemia with a previously "normal" karyotype, 18% exhibited a previously undetected CNA, whereas in the (few) t-AML with a normal karyotype, the rate was 50%. Several minimal critical regions (MCRs) were found in t-AML and p-AML. No common MCRs were found in the two groups. In t-AML a 40 kb deleted MCR pointed to RUNX1 on 21q22, a gene coding for a transcription factor implicated in frequent rearrangements in leukemia and in familial thrombocytopenia. In de novo AML, a 1 Mb MCR harboring ERG and ETS2 was observed from patients with complex aCGH profiles. High resolution cytogenomics obtained by aCGH and similar techniques already published allowed us to characterize numerous non random chromosome abnormalities. This work supports the hypothesis that they can be classified into several categories: abnormalities common to all AML; those more frequently found in t-AML and those specifically found in p-AML.
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PMID:Chromosomal minimal critical regions in therapy-related leukemia appear different from those of de novo leukemia by high-resolution aCGH. 2133 20

The outcome of treating chronic myeloid leukemia (CML) with imatinib mesylate (IM) is inferior when therapy is commenced in late chronic or accelerated phase as compared to early chronic phase. This may be attributed to additional genomic alterations that accumulate during disease progression. We sought to identify such lesions in patients showing suboptimal response to IM by performing array-CGH analysis on 39 sequential samples from 15 CML patients. Seventy-four cumulative copy number alterations (CNAs) consisting of 35 losses and 39 gains were identified. Alterations flanking the ABL1 and BCR genes on chromosomes 9 and 22, respectively, were the most common identified lesions with 5 patients losing variable portions of 9q34.11 proximal to ABL1. Losses involving 1p36, 5q31, 17q25, Y and gains of 3q21, 8q24, 22q11, Xp11 were among other recurrent lesions identified. Aberrations were also observed in individual patients, involving regions containing known leukemia-associated genes; CDKN2A/2B, IKZF1, RB1, TLX1, AFF4. CML patients in late stages of their disease, harbor pre-existing and evolving sub-microscopic CNAs that may influence disease progression and IM response.
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PMID:Identification of copy number alterations by array comparative genomic hybridization in patients with late chronic or accelerated phase chronic myeloid leukemia treated with imatinib mesylate. 2138 93

During the past decade, array CGH has been applied to study copy number alterations in the genome in human leukemia in relation to prediction of prognosis or responsiveness to therapy. In the first segment of this review, we will focus on the identification of acquired mutations by array CGH, followed by studies on the pathogenesis of leukemia associated with germline genetic variants, phenotypic presentation and response to treatment. In the last section, we will discuss constitutional genomic aberrations causally related to myeloid leukemogenesis.
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PMID:Array CGH in human leukemia: from somatics to genetics. 2189 61

Chromosomal abnormalities, like deletions, amplifications, inversions or translocations, are recurrent features in haematological malignancies. However, the precise molecular breakpoints are frequently not determined. Here we describe a rapid analysis of genetic imbalances combining fine tiling comparative genomic hybridization (FT-CGH) and ligation-mediated PCR (LM-PCR). We clarified an inv(14)(q11q32) in a case of T cell acute lymphoblastic leukaemia with a breakpoint in the TRA/D in 68% of cells detected by fluorescence in situ hybridization. FT-CGH showed several mono- and biallelic losses within TRA/D. LM-PCR disclosed a TRA/D rearrangement on one allele. The other allele revealed an inv(14)(q11q32), joining TRDD2 at 21,977,000 of 14q11 together with the IGH locus at 105,948,000 and 3'-sequence of TRAC at 22,092,000 joined together with IGHV4-61 at 106,166,000. This sensitive approach can unravel complex chromosomal abnormalities in patient samples with a limited amount of aberrant cells and may lead to better diagnostic and therapeutic options.
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PMID:Fast approach for clarification of chromosomal aberrations by using LM-PCR and FT-CGH in leukaemic sample. 2198 43

Among 4,780 consecutive adult acute lymphoblastic/myeloblastic leukemia patients, we identified 117 (2.4%) patients with mixed-phenotype acute leukemia fulfilling WHO 2008 criteria; these were classified as: Blymphoid+ myeloid (n=64), T-lymphoid+myeloid (n=38), B+T-lymphoid (n=14) and trilineage (n=1). Of 92 patients karyotyped, 59 were abnormal and were classified as: complex (22 of 92), t(9;22)(q34;q11) (14 of 92), monosomy 7 (7 of 92), polysomy 21 (7 of 92), t(v;11q23) (4 of 92), t(10;11)(p15;q21) (3 of 92), while STIL-TAL1 fusion was detected in one (T+My) patient. After investigating common acute leukemia-related mutations in 17 genes, 12 of 31 (39%) patients were found to have at least one mutation, classified with: IKZF1 deletion (4 of 31), and EZH2 (3 of 31), ASXL1 (3 of 31), ETV6 (2 of 31), NOTCH1 (1 of 31), and TET2 (1 of 31) mutations. Array-CGH revealed genomic deletions of CDKN2A (4 of 12), IKZF1 (3 of 12), MEF2C (2 of 12), BTG1 (2 of 12), together with BCOR, EBF1, K-RAS, LEF1, MBNL1, PBX3, and RUNX1 (one of 12 each). Our results indicate that mixed-phenotype acute leukemia is a complex entity with heterogeneous clinical, immunophenotypic, cytogenetic, and molecular genetic features.
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PMID:Clinical, immunophenotypic, cytogenetic, and molecular genetic features in 117 adult patients with mixed-phenotype acute leukemia defined by WHO-2008 classification. 2258 Oct 2


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