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| 2. |
- Castor, Anders, et al.
(författare)
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Distinct patterns of hematopoietic stem cell involvement in acute lymphoblastic leukemia
- 2005
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 11:6, s. 630-637
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Tidskriftsartikel (refereegranskat)abstract
- The cellular targets of primary mutations and malignant transformation remain elusive in most cancers. Here, we show that clinically and genetically different subtypes of acute lymphoblastic leukemia (ALL) originate and transform at distinct stages of hematopoietic development. Primary ETV6-RUNX1 (also known as TEL-AML1) fusions and subsequent leukemic transformations were targeted to committed B-cell progenitors. Major breakpoint BCR-ABL1 fusions (encoding P210 BCR-ABL1) originated in hematopoietic stem cells (HSCs), whereas minor BCR-ABL1 fusions (encoding P190 BCR-ABL1) had a B-cell progenitor origin, suggesting that P190 and P210 BCR-ABL1 ALLs represent largely distinct tumor biological and clinical entities. The transformed leukemia-initiating stem cells in both P190 and P210 BCR-ABL1 ALLs had, as in ETV6-RUNX1 ALLs, a committed B progenitor phenotype. In all patients, normal and leukemic repopulating stem cells could successfully be separated prospectively, and notably, the size of the normal HSC compartment in ETV6-RUNX1 and P190 BCR-ABL1 ALLs was found to be unaffected by the expansive leukemic stem cell population.
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| 4. |
- Lundin, Catarina, et al.
(författare)
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Tiling resolution array CGH of dic(7;9)(p11 approximately 13;p11 approximately 13) in B-cell precursor acute lymphoblastic leukemia reveals clustered breakpoints at 7p11.2 approximately 12.1 and 9p13.1.
- 2007
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Ingår i: Cytogenetic and Genome Research. - : S. Karger AG. - 1424-859X .- 1424-8581. ; 118:1, s. 13-18
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Tidskriftsartikel (refereegranskat)abstract
- The dic( 7; 9)( p11 similar to 13; p11 similar to 13) is a recurrent chromosomal abnormality in acute lymphoblastic leukemia (ALL), mainly of B-lineage. Although more than 20 dic(7; 9)-positive ALLs have been reported to date, the molecular genetic consequences of this aberration are unknown. We performed tiling resolution (32K) genome-wide array-based comparative genomic hybridization ( array CGH) analysis of three cases with dic(7; 9) in order to characterize the breakpoints on 7p and 9p. The analysis showed a clustering of breakpoints within 9p13.1 in all three cases and within 7p11.2 in two cases; the array CGH revealed two different breakpoints - 7p12.1 and 7p14.1 - in the remaining case. Based on these findings the abnormality should hence be designated dic(7; 9)(p11.2 similar to 12.1; p13.1). Locus-specific fluorescence in situ hybridization analysis of one of the cases narrowed down the 7p11.2 breakpoint to a < 500-kb segment in this sub-band, a region containing three known genes. Unfortunately, lack of material precluded further molecular genetic studies, and it thus remains unknown whether the pathogenetically important outcome of the dic(7; 9) is formation of a chimeric gene or loss of 7p and/or 9p material. Copyright (c) 2007 S. Karger AG, Basel.
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| 5. |
- Nilsson, Lars, et al.
(författare)
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The molecular signature of MDS stem cells supports a stem-cell origin of 5q-myelodysplastic syndromes
- 2007
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 110:8, s. 3005-3014
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Tidskriftsartikel (refereegranskat)abstract
- Global gene expression profiling of highly purified 5q-deleted CD34+CD38–Thy1+ cells in 5q– myelodysplastic syndromes (MDSs) supported that they might originate from and outcompete normal CD34+CD38–Thy1+ hematopoietic stem cells. Few but distinct differences in gene expression distinguished MDS and normal stem cells. Expression of BMI1, encoding a critical regulator of self-renewal, was up-regulated in 5q– stem cells. Whereas multiple previous MDS genetic screens failed to identify altered expression of the gene encoding the myeloid transcription factor CEBPA, stage-specific and extensive down-regulation of CEBPA was specifically observed in MDS progenitors. These studies establish the importance of molecular characterization of distinct stages of cancer stem and progenitor cells to enhance the resolution of stage-specific dysregulated gene expression.
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| 7. |
- Panagopoulos, Ioannis, et al.
(författare)
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Fusion of NUP98 and the SET binding protein 1 (SETBP1) gene in a paediatric acute T cell lymphoblastic leukaemia with t(11;18)(p15;q12).
- 2007
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 136:2, s. 294-296
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Tidskriftsartikel (refereegranskat)abstract
- Three NUP98 chimaeras have previously been reported in T cell acute lymphoblastic leukaemia (T-ALL): NUP98/ADD3, NUP98/CCDC28A, and NUP98/RAP1GDS1. We report a T-ALL with t(11;18)(p15;q12) resulting in a novel NUP98 fusion. Fluorescent in situ hybridisation showed NUP98 and SET binding protein 1(SETBP1) fusion signals; other analyses showed that exon 12 of NUP98 was fused in-frame with exon 5 of SETBP1. Nested polymerase chain reaction did not amplify the reciprocal SETBP1/NUP98, suggesting that NUP98/SETBP1 transcript is pathogenetically important. SETBP1 has previously not been implicated in leukaemias; however, it encodes a protein that specifically interacts with SET, fused to NUP214 in a case of acute undifferentiated leukaemia.
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| 8. |
- Panagopoulos, Ioannis, et al.
(författare)
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MLL/GAS7 fusion in a pediatric case of t(11;17)(q23;p13)-positive precursor B-cell acute lymphoblastic leukemia
- 2006
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Ingår i: Haematologica. - 1592-8721. ; 91:9, s. 1287-1288
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- AML/GAS7, resulting from t(11;17)(q23;p13), has been reported in one case of treatment-related acute myeloid leukemia (AML). We present a de novo case of t(11;17)-positive pediatric acute lymphoblastic leukemia. Fluorescent in situ hybridization and reverse transcriptase polymerase chain reaction analyses revealed an MLL/GAS7 chimera identical to the one previously described in AML. The molecular genetic features of MLL/GAS7 and the clinical impact of t(11;17) are discussed.
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| 9. |
- Paulsson, Kajsa, et al.
(författare)
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Evidence for a single-step mechanism in the origin of hyperdiploid childhood acute lymphoblastic leukemia
- 2005
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 44:2, s. 113-122
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Tidskriftsartikel (refereegranskat)abstract
- High hyperdiploidy (>50 chromosomes) in childhood acute lymphoblastic leukemia (ALL) is characterized by nonrandom multiple trisomies and tetrasomies involving in particular chromosomes X, 4, 6, 8, 10, 14, 17, 18, and 21. This characteristic karyotypic pattern, the most common in pediatric ALL, may arise via a tetraploid state with subsequent loss of chromosomes, by sequential gains of chromosomes in consecutive cell divisions, or by simultaneous gain of chromosomes in a single mitosis. These alternatives may be distinguished by investigation of the allelic ratios of loci on the tetrasomic and disomic chromosomes. Previous studies of tetrasomy 21 and of the occurrence of uniparental disomies (UPDs) have suggested that the most likely mechanism is simultaneous gain. However, the other pathways have not been definitely excluded because complete analyses of all disomies and tetrasomies have never been performed. In the present study, we investigated 27 hyperdiploid ALLs by using 58 polymorphic microsatellite markers mapped to 23 of the 24 human chromosomes. Twenty-six tetrasomies were analyzed (involving chromosomes X, 8, 10, 14, 18, and 21), and the frequency of UPDs was determined in 10 cases. In total, 200 chromosomes were studied. Equal allele dosage was observed in 24 of 26 tetrasomies, and only 7 UPDs were found. These data strongly suggest that hyperdiploidy in childhood ALL generally arises by a simultaneous gain of all additional chromosomes in a single abnormal mitosis. © 2005 Wiley-Liss, Inc.
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