Ph-positive chronic myeloid leukemia with near-haploid conversion in vivo and establishment of a continuously growing cell line with similar cytogenetic pattern

Andersson, Börje S.; Beran, Miloslav; Pathak, Sen; Goodacre, Angela; Barlogie, Barthel; McCredie, Kenneth B.

doi:10.1016/0165-4608(87)90116-6

Cited by 51 publications

(40 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A NHG is a relatively rare phenomenon in cancer (Mandahl et al, ) and has been described in chondrosarcoma (Bovee et al, ), acute lymphoblastic leukemia (Safavi et al, ; Holmfeldt et al, ), chronic myeloid leukemia (Andersson et al, ; Gancberg et al, ) and has occasionally been found in plasmocytoma (Kristoffersson et al, ), malignant fibrous histiocytoma (Aspberg et al, ) and peritoneal mesothelioma (Sukov et al, ). More recently, we showed that a NHG is a common feature of the oncocytic variant of follicular thyroid carcinoma (FTC‐OV; Corver et al, ).…”

Section: Discussionmentioning

confidence: 99%

Near‐haploidization significantly associates with oncocytic adrenocortical, thyroid, and parathyroid tumors but not with mitochondrial DNA mutations

Corver

Wezel

Molenaar

et al. 2014

Genes Chromosomes & Cancer

View full text Add to dashboard Cite

Mitochondrial-rich oncocytic thyroid tumors frequently show near-haploidization and endoreduplication (masked haploidization), which manifests as a near-homozygous genome (NHG). We now extend this investigation to include adrenocortical cancer and parathyroid carcinoma (PaTC), which we studied for a NHG in association with mitochondrial DNA mutations. Sixty endocrine tumors from 59 patients were studied, including 46 thyroid tumor samples of varying histology, 11 adrenocortical cancers, and 3 PaTCs. Genome-wide SNP array analysis and DNA content analysis were combined to determine the chromosomal dosage (allelic state). The entire mitochondrial genome was also studied for mutations. In addition, tumors were characterized for somatic mutations in a subset of genes that are directly or indirectly implicated in cellular metabolism. In addition to a subset of thyroid cancers (n = 5), a NHG was also observed in 1 of 3 PaTCs and 6 of 11 adrenocortical cancers. All but one of the tumors with a NHG (n = 12) showed oncocytic metaplasia (P = 0.0001, two-tailed Fisher's exact). One or more damaging or disrupting mtDNA mutations were found in 68% (41/60) of tumor samples. No correlation was found between mtDNA mutations and the oncocytic phenotype or a NHG, and none of the mutations in nuclear encoded genes correlated with the oncocytic phenotype or a NHG. A subset of oncocytic tumors of the thyroid, parathyroid, and adrenocortical carcinomas carries a NHG. Although damaging/disrupting mtDNA mutations are frequently found in oncocytic and nononcocytic endocrine tumors, neither correlates with a NHG phenotype nor with an oncocytic phenotype.

show abstract

Section: Discussionmentioning

confidence: 99%

Near‐haploidization significantly associates with oncocytic adrenocortical, thyroid, and parathyroid tumors but not with mitochondrial DNA mutations

Corver

Wezel

Molenaar

et al. 2014

Genes Chromosomes & Cancer

View full text Add to dashboard Cite

show abstract

“…Near-haploid karyotypes have been reported in rare human tumors and leukemias [43] and a heterogeneous (mixed ploidy) cell line (KBM7) was established from the bone marrow of a patient with a near-haploid chronic myeloid leukemia [44]. Although around half of the cells in the initial cultures were near-haploid (apart from disomy of chromosome 8), cells with a diploid or greater DNA content tended to outgrow them with continuous passage, rendering this cell line initially unsuitable for somatic cell genetics.…”

Section: Functional Genomics In Haploid Mammalian Cellsmentioning

confidence: 99%

Functional genomic screening approaches in mechanistic toxicology and potential future applications of CRISPR-Cas9

Shen¹,

McHale²,

Smith³

et al. 2015

Mutation Research/Reviews in Mutation Research

View full text Add to dashboard Cite

Characterizing variability in the extent and nature of responses to environmental exposures is a critical aspect of human health risk assessment. Chemical toxicants act by many different mechanisms, however, and the genes involved in adverse outcome pathways (AOPs) and AOP networks are not yet characterized. Functional genomic approaches can reveal both toxicity pathways and susceptibility genes, through knockdown or knockout of all non-essential genes in a cell of interest, and identification of genes associated with a toxicity phenotype following toxicant exposure. Screening approaches in yeast and human near-haploid leukemic KBM7 cells, have identified roles for genes and pathways involved in response to many toxicants but are limited by partial homology among yeast and human genes and limited relevance to normal diploid cells. RNA interference (RNAi) suppresses mRNA expression level but is limited by off-target effects (OTEs) and incomplete knockdown. The recently developed gene editing approach called clustered regularly interspaced short palindrome repeats-associated nuclease (CRISPR)-Cas9, can precisely knock-out most regions of the genome at the DNA level with fewer OTEs than RNAi, in multiple human cell types, thus overcoming the limitations of the other approaches. It has been used to identify genes involved in the response to chemical and microbial toxicants in several human cell types and could readily be extended to the systematic screening of large numbers of environmental chemicals. CRISPR-Cas9 can also repress and activate gene expression, including that of non-coding RNA, with near-saturation, thus offering the potential to more fully characterize AOPs and AOP networks. Finally, CRISPR-Cas9 can generate complex animal models in which to conduct preclinical toxicity testing at the level of individual genotypes or haplotypes. Therefore, CRISPR-Cas9 is a powerful and flexible functional genomic screening approach that can be harnessed to provide unprecedented mechanistic insight in the field of modern toxicology.

show abstract

“…Interestingly, hypodiploid, including rare near haploid tumor karyotypes, have been reported. Near haploid tumor cells have been observed in rare cases of leukemia [43-49], and have been less frequently reported in solid tumors [50-52]. Loss of chromosomes appears to be the primary event in near haploid acute lymphoid leukemia and correlates with poor prognosis [44,53].…”

Section: Reviewmentioning

confidence: 99%

“…Cells with near haploid and hypodiploid karyotypes have been adapted to growth in culture from a partially haploid chronic myeloid leukemia [43]. Apparently, these cultures were obtained at the blast phase after a long benign phase and repeated chemotherapeutic treatment suggesting significant selection of tumor cells before cultures were established.…”

Section: Reviewmentioning

confidence: 99%

Haploid genomes illustrate epigenetic constraints and gene dosage effects in mammals

Leeb

Wutz

2013

Epigenetics & Chromatin

View full text Add to dashboard Cite

Sequencing projects have revealed the information of many animal genomes and thereby enabled the exploration of genome evolution. Insights into how genomes have been repeatedly modified provide a basis for understanding evolutionary innovation and the ever increasing complexity of animal developmental programs. Animal genomes are diploid in most cases, suggesting that redundant information in two copies of the genome increases evolutionary fitness. Genomes are well adapted to a diploid state. Changes of ploidy can be accommodated early in development but they rarely permit successful development into adulthood. In mammals, epigenetic mechanisms including imprinting and X inactivation restrict haploid development. These restrictions are relaxed in an early phase of development suggesting that dosage regulation appears less critical. Here we review the recent literature on haploid genomes and dosage effects and try to embed recent findings in an evolutionary perspective.

show abstract

Ph-positive chronic myeloid leukemia with near-haploid conversion in vivo and establishment of a continuously growing cell line with similar cytogenetic pattern

Cited by 51 publications

References 12 publications

Near‐haploidization significantly associates with oncocytic adrenocortical, thyroid, and parathyroid tumors but not with mitochondrial DNA mutations

Near‐haploidization significantly associates with oncocytic adrenocortical, thyroid, and parathyroid tumors but not with mitochondrial DNA mutations

Functional genomic screening approaches in mechanistic toxicology and potential future applications of CRISPR-Cas9

Haploid genomes illustrate epigenetic constraints and gene dosage effects in mammals

Contact Info

Product

Resources

About