Appearance of Ph negative recipient clones in chronic myeloid leukemia patients following bone marrow transplantation

Williams, S; Williams, Jeffrey; Barnard, D. L.; Mason, M. K.

doi:10.1016/0165-4608(92)90101-d

Cancer Genetics and Cytogenetics

1992

DOI: 10.1016/0165-4608(92)90101-d

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Appearance of Ph negative recipient clones in chronic myeloid leukemia patients following bone marrow transplantation

S Williams

Jeffrey Williams²,

D. L. Barnard

et al.

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Cited by 3 publications

(2 citation statements)

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“…On the other hand, it is possible that the trisomy 8 clone was present in cells belonging not to the C M L population, but to a secondary myelodysplastic syndrome, which could be the result of previous treatments (HU, busulfan, melphalan). We are in (Williams et al, 1992). T h i s phenomenon seems to be more frequent among PHA-stimulated circulating T-lymphocyte metaphase cells than in BM cells.…”

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confidence: 76%

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A second case of trisomy 8 in philadelphia chromosome (Ph)‐negative cells during the course of Ph‐positive chronic myelocytic leukemia

Bilhou-Nabéra

Marit

Devianne

et al. 1993

Genes Chromosomes & Cancer

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confidence: 76%

“…We are in (Williams et al, 1992). T h i s phenomenon seems to be more frequent among PHA-stimulated circulating T-lymphocyte metaphase cells than in BM cells.…”

mentioning

confidence: 83%

A second case of trisomy 8 in philadelphia chromosome (Ph)‐negative cells during the course of Ph‐positive chronic myelocytic leukemia

Bilhou-Nabéra

Marit

Devianne

et al. 1993

Genes Chromosomes & Cancer

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The Occurrence of Philadelphia Chromosome (Ph) Negative Leukemia after Hematopoietic Stem Cell Transplantation for Ph Positive Chronic Myeloid Leukemia: Implications for Disease Monitoring and Treatment

Kwong

2003

Leukemia & Lymphoma

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Chronic myeloid leukemia (CML) is a clonal neoplastic disorder, characterized by t(9;22)(q34;q11) that results in the formation of the Philadelphia chromosome (Ph) and the BCR/ABL fusion gene. Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for CML. Much of its therapeutic efficacy is attributed to a graft-versus-leukemia (GVL) effect exerted by donor-derived lymphoid cells against the Ph positive (Ph+) clone. Post-HSCT monitoring by cytogenetic and molecular detection of the Ph+ clone is necessary, so that pre-emptive immunologic or pharmacologic treatment may be administered at an early stage of relapse. However, under rare circumstances a second Ph negative (Ph-) leukemia may evolve post-HSCT. The pathogenetic possibilities included leukemia arising from donor-derived hematopoietic stem cells (HSCs), or transformation of residual recipient-derived Ph- HSCs that have survived the conditioning chemotherapy and radiotherapy. Recipient-derived Ph- leukemia may be related to genetic alterations that precede the onset of CML, or myelotoxic effects of the HSCT conditioning regimen. The diagnosis of Ph- relapses requires detailed investigations by conventional karyotyping, fluorescence in-situ hybridization (FISH), and molecular analysis; as well as chimerism studies that help to document the donor or recipient origin of the leukemia. Although uncommonly reported in the past, Ph- relapses may in fact be more frequent if leukemic relapses post-HSCT are more thoroughly evaluated with these investigations. The recognition of Ph- relapses are important in several ways. Ph- relapses cannot be identified by monitoring investigations targeting the Ph+ clone, so that the early detection of Ph- leukemia is usually not possible. Furthermore, Ph- relapses will not respond to therapeutic strategies effective against the Ph+ CML clone.

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Ionizing radiation-induced instant pairing of heterochromatin of homologous chromosomes in human cells

Abdel-Halim

Imam²,

Badr³

et al. 2004

Cytogenet Genome Res

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Using fluorescence in situ hybridization with human band-specific DNA probes we examined the effect of ionizing radiation on the intra-nuclear localization of the heterochromatic region 9q12→q13 and the euchromatic region 8p11.2 of similar sized chromosomes 9 and 8 respectively in confluent (G₁) primary human fibroblasts. Microscopic analysis of the interphase nuclei revealed colocalization of the homologous heterochromatic regions from chromosome 9 in a proportion of cells directly after exposure to 4 Gy X-rays. The percentage of cells with paired chromosomes 9 gradually decreased to control levels during a period of one hour. No significant changes in localization were observed for chromosome 8. Using 2-D image analysis, radial and inter-homologue distances were measured for both chromosome bands. In unexposed cells, a random distribution of the chromosomes over the interphase nucleus was found. Directly after irradiation, the average inter-homologue distance decreased for chromosome 9 without alterations in radial distribution. The percentage of cells with inter-homologue distance <3 µm increased from 11% in control cells to 25% in irradiated cells. In contrast, irradiation did not result in significant changes in the inter-homologue distance for chromosome 8. Colocalization of the heterochromatic regions of homologous chromosomes 9 was not observed in cells irradiated on ice. This observation, together with the time dependency of the colocalization, suggests an underlying active cellular process. The biological relevance of the observed homologous pairing remains unclear. It might be related to a homology dependent repair process of ionizing radiation induced DNA damage that is specific for heterochromatin. However, also other more general cellular responses to radiation-induced stress or change in chromatin organization might be responsible for the observed pairing of heterochromatic regions.

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Appearance of Ph negative recipient clones in chronic myeloid leukemia patients following bone marrow transplantation

Cited by 3 publications

References 16 publications

A second case of trisomy 8 in philadelphia chromosome (Ph)‐negative cells during the course of Ph‐positive chronic myelocytic leukemia

A second case of trisomy 8 in philadelphia chromosome (Ph)‐negative cells during the course of Ph‐positive chronic myelocytic leukemia

The Occurrence of Philadelphia Chromosome (Ph) Negative Leukemia after Hematopoietic Stem Cell Transplantation for Ph Positive Chronic Myeloid Leukemia: Implications for Disease Monitoring and Treatment

Ionizing radiation-induced instant pairing of heterochromatin of homologous chromosomes in human cells

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