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At least 145 records · Page 8Linked to original sources
PubMed1979

Clonal evolution of marker chromosomes in a case of myelofibrosis with myeloid metaplasia and myeloblastic transformation.

The diverse spectrum of acquired chromosome abnormalities in a female patient with myelofibrosis and myeloid metaplasia is described. A sequence of karyotypic evolution involving a ring chromosome is postulated. The terminal clinical picture was unusual in that there was obstructive renal failure from extramedullary myeloblastic transformation and infiltration of the bladder, and this was also present in other sites. Initially neutrophils showed low alkaline phosphatases activity but latterly two distinct populations in which cells had either high activity or none.

Alkaline Phosphatase↗
PubMed1976

Unusual clonal evolution in a case of chronic myelogenous leukemia.

Several unusual cytogenetic changes have occurred during the evolution of chronic myelogenous leukemia in a 32-year-old white male with this disease for 8 years. The first appearance of a hypodiploid cell line containing a dicentric marker occurred 2 years after diagnosis and this line was eliminated by several courses of therapy with hydroxyurea. A second clone, which had a partial deletion of the long arm of one of the number 8 chromosomes (8q-) was noted a year later, but this line has been refractory to intensive combination chemotherapy.

Adult↗
PubMed2001

Variable heavy-chain gene analysis of follicular lymphomas: subclone selection rather than clonal evolution over time.

To investigate B-cell receptor evolution in follicular lymphomas (FLs), immunoglobulin variable heavy chain (V(H)) gene regions of 3 FLs were analyzed at different time points. One FL with a high somatic mutation load and intraclonal V(H) gene diversity was investigated in situ. V(H) gene transcripts were amplified and sequenced from samples of approximately 50 tumor cells isolated from frozen tissue sections by laser microdissection. Interestingly, the mutation pattern of the prevalent subclone in the relapse biopsy was virtually identical to that of a subclone isolated by microdissection from the presentation biopsy 9 years earlier. In a second FL, proof was obtained that the subclone that dominated the relapse sample had already been present in the initial biopsy. The finding that subclones found in the relapses of these FLs had not evolved over time but were preexistent, challenges the concept of antigen-driven B-cell receptor evolution during disease course.

Cell Transformation, Neoplastic↗
PubMed2002

Initiation of human astrocytoma by clonal evolution of cells with progressive loss of p53 functions in a patient with a 283H TP53 germ-line mutation: evidence for a precursor lesion.

Little is known about the genetic and molecular events leading to the early stages of human astrocytoma formation. To examine this issue, we analyzed the significance of sequential accumulation of two somatic point mutations (R267W and E258D) in the TP53 gene during the initiation of astrocytoma in a patient born with a single germ-line p53 point mutation (R283H). We adapted a p53 transcriptional assay in yeast to establish the temporal occurrence and allelic distribution of the p53 mutations present in the patient and characterized these mutations through functional assays and structural modeling. Our results show that the first somatic mutation occurred at codon 267 on the p53 allele harboring the germ-line mutation R283H, whereas the second somatic mutation occurred in the remaining wild-type (wt) allele at codon 258. These two mutations induced the formation of tumor cells with the genotype p53(267W+283H/258D), which comprised 70% of the cells in the primary WHO grade II astrocytoma. Another 8% of cells within the tumor had the partially mutated genotype p53(267W+283H/WT) and represented the remnants of a clinically undetectable intermediate stage of astrocytic neoplastic transformation. The remaining 22% of cells had the constitutive p53(283H/WT) genotype and likely consisted of nontumor cells. Functional analysis of the p53 alleles present in the patient's tumor indicated that the germ-line p53(R283H) could transactivate the CDKN1A((p21, WAF1, cip1, SDI1)) but not the BAX gene and retained the ability to induce growth arrest of human glioblastoma cells. The p53(R267W+R283H) and p53(E258D) were incapable of transactivating either promoter or inducing growth arrest. Modeling of p53 interaction with DNA suggests that R283H mutation may weaken the sequence-specific interaction of p53 lysine 120 with the BAX gene but not the CDKN1A p53-responsive elements. Taken together, these results have characterized, for the first time, the genetic events defining a clinically undetectable precursor lesion leading to a grade II astrocytoma. They also suggest that astrocytoma initiation in this patient resulted from monoclonal evolution driven by a sequential loss of proapoptotic and growth arrest functions of p53.

Adult↗
PubMed1988

Transposition of the oncogene c-ets-1 in a t(11;19)(q23;p13) cell line transient during clonal evolution of blast crisis chronic myeloid leukemia.

A patient with Ph-negative chronic myeloid leukemia showed active karyotypic evolution when he entered blast crisis. One cell line, which predominated briefly in an accelerated myeloid phase, was characterized by the t(11;19)(q23;p13). Chromosome in situ hybridization demonstrated movement of the oncogene c-ets-1 from the der (11q-) to the der (19p+). The breakpoint at 19p13 was in the vicinity of the human insulin receptor gene locus (INSR). No rearrangements of the c-ets and INSR genes were found in Southern blot analyses. Myeloid lineage was indicated by cell morphology and absence of immunoglobulin JH gene rearrangement and was supported by loss of the germ line bcr-3' gene. Chromosome rearrangements involving 11q23 and movement of c-ets-1 characterize monocytic and lymphoid leukemias and have not previously been reported in myeloid blast crisis of chronic myeloid leukemia.

Cell Transformation, Neoplastic↗