Mutagen exposures and chromosome 3 aberrations in acute myelocytic leukemia

Lindquist, Ragnhild; Forsblom, AM; Öst, Åke; Gahrton, Gösta

doi:10.1038/sj.leu.2401622

Cited by 12 publications

(6 citation statements)

References 51 publications

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“…Numerical and structural changes of chromosome 3, such as monosomy 3, trisomy 3 and del(3)(p13p21) etc. in AML patients have also been reported recently to be associated with occupational exposure to organic solvents and/or petroleum products (Lindquist et al, 2000). Loss of E-group chromosomes, including chromosomes 17 and 18, was detected in several studies (Golomb et al, 1982;Groupe, 1984).…”

Section: F Chromosome Changes In Leukemia Patients With Likely Priormentioning

confidence: 81%

The Nature of Chromosomal Aberrations Detected in Humans Exposed to Benzene

Zhang¹,

Eastmond

Smith³

2002

Critical Reviews in Toxicology

151

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Section: F Chromosome Changes In Leukemia Patients With Likely Priormentioning

confidence: 81%

The Nature of Chromosomal Aberrations Detected in Humans Exposed to Benzene

Zhang¹,

Eastmond

Smith³

2002

Critical Reviews in Toxicology

151

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“…This location is a fragile site region of chromosome 3, and is mainly known to be affected in therapy-related adult AML (30). Chromosome 3 aberrations are rare in pediatrics, but do occur as translocations, inversions and deletions (30, 31). These genetic alterations may contribute to aberrant expression of EphB1 in AML patients.…”

Section: Discussionmentioning

confidence: 99%

EphB1 Suppression in Acute Myelogenous Leukemia: Regulating the DNA Damage Control System

Kampen

Scherpen

Garcia‐Manero

et al. 2015

Molecular Cancer Research

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Loss of ephrin receptor (EphB1) expression may associate with aggressive cancer phenotypes; however, the mechanism of action remains unclear. To gain detailed insight into EphB1 function in acute myelogenous leukemia (AML), comprehensive analysis of EphB1 transcriptional regulation was conducted. In AML cells, EphB1 transcript was inversely correlated with EphB1 promoter methylation. The presence of EphB1 allowed EfnB1 ligand–mediated p53 DNA binding, leading to restoration of the DNA damage response (DDR) cascade by the activation of ATR, Chk1, p53, p21, p38, CDK1tyr15, and Bax, and downregulation of HSP27 and Bcl2. Comparatively, reintroduction of EphB1 expression in EphB1-methylated AML cells enhanced the same cascade of ATR, Chk1, p21, and CDK1tyr15, which consequently enforced programmed cell death. Interestingly, in pediatric AML samples, EphB1 peptide phosphorylation and mRNA expression were actively suppressed as compared with normal bone marrow, and a significant percentage of the primary AML specimens had EphB1 promoter hyper-methylation. Finally, EphB1 repression associated with a poor overall survival in pediatric AML. Combined, the contribution of EphB1 to the DDR system reveals a tumor-suppressor function for EphB1 in pediatric AML. Implications The tumor-suppressor function of EphB1 is clinically relevant across many malignancies, suggesting that EphB1 is an important regulator of common cancer cell trans forming pathways.

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“…They are present in 2% of patients with AML, as well as patients with MDS, and in the blastic phase of CML (Bitter et al, 1985;Lindquist et al, 2000). A strong association with trilineage myelodysplasia including abnormalities of the megakaryocytic lineage has been reported.…”

Section: Q21q26 Subsetmentioning

confidence: 99%

Rare recurring balanced chromosome abnormalities in therapy‐related myelodysplastic syndromes and acute leukemia: Report from an International Workshop†

Block

Carroll

Hagemeijer³

et al. 2002

Genes Chromosomes & Cancer

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Seventy-seven patients were identified with Rare recurring (excluding 11q23, 21q22, inv(16), and t(15;17)) chromosome abnormalities among 511 patients with treatment-related myelodysplastic syndromes and acute leukemia accepted from centers in the United States, Europe, and Japan. The abnormality subsets included 3q21q26 (17 patients), 11p15 (17 patients), t(9;22)(q34;q11) (10 patients), 12p13 (9 patients), t(8;16)(p11;p13) (9 patients), and an "other" subset, which included t(6;9)(p23;q34) (3 patients), t(10;11)(p13;q13 approximately q21) (3 patients), t(1;17)(p36;q21) (2 patients), t(8;14)(q24;q32) (2 patients), t(11;19)(q13;q13) (2 patients), t(1;3)(p36;q21) (2 patients), and t(3;5)(q21;q31) (1 patient). Increased karyotypic complexity with additional balanced and unbalanced rearrangements was observed in 70% of cases. Among 54 cases with secondary abnormalities, chromosome 5 and/or 7 abnormalities were observed in 59%. The most frequent primary diseases were breast cancer (24 cases), Hodgkin disease (14 cases), non-Hodgkin lymphoma (10 cases), and de novo ALL (5 cases). Thirty-seven patients received alkylating agents plus topoisomerase II inhibitors with or without radiation therapy. The presenting diagnosis was t-AML in 47 cases, t-MDS in 23 cases (10 progressed to t-AML), and t-ALL in seven cases, five of whom had a t(9;22). The median latency time from initiation of original therapy to therapy-related disease diagnosis was quite long (69 months), and the overall median survival from the date of therapy-related disease diagnosis was very short (7 months). The 1-year survival rate was 34 +/- 7%, with no significant differences among subsets. Comparison with previously reported cases showed increased karyotypic complexity and adult presentation of pediatric-associated chromosome abnormalities.

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Mutagen exposures and chromosome 3 aberrations in acute myelocytic leukemia

Cited by 12 publications

References 51 publications

The Nature of Chromosomal Aberrations Detected in Humans Exposed to Benzene

The Nature of Chromosomal Aberrations Detected in Humans Exposed to Benzene

EphB1 Suppression in Acute Myelogenous Leukemia: Regulating the DNA Damage Control System

Rare recurring balanced chromosome abnormalities in therapy‐related myelodysplastic syndromes and acute leukemia: Report from an International Workshop†

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