Distinguishing between the Chromosomes involved in Down's Syndrome (Trisomy 21) and Chronic Myeloid Leukaemia (Ph1) by Fluorescence

O'riordan, M. L.; Robinson, Jacqueline; Buckton, K. E.; Evans, H. J.

doi:10.1038/230167a0

Cited by 124 publications

(20 citation statements)

References 8 publications

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“…Normal or increased NAP activity and persisting Ph'-positivity is also seen in some cases of CGL after acute transformation (King et al, 1962;Hammouda, Quaglino, and Hayhoe, 1964). Other hypotheses which sought to explain elevated NAP scores in Down's syndrome and decreased scores in CGL as dose-effects of the NAP gene(s) were early seen to be unsatisfactory (King et al, 1962) and later became untenable with the demonstration (O'Riordan, Robinson, Buckton, and Evans, 1971) that the Ph' anomaly involves a chromosome different from that which is present in triplicate in Down's syndrome.…”

Section: Effects Of Splenectomy Upon Nap Scorementioning

confidence: 99%

Neutrophil alkaline phosphatase score in chronic granulocytic leukaemia: effects of splenectomy and antileukaemic drugs.

Spiers¹,

Liew²,

Baikie³

1975

J Clin Pathol

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SYNOPSIS Staining with naphthol AS phosphate and Fast Blue BB salt has been used for the estimation of neutrophil alkaline phosphatase (NAP) scores in patients with chronic granulocytic leukaemia (CGL). The very low scores found at diagnosis rise when the disease is treated, and there is some inverse correlation between the NAP score and the absolute neutrophil count. Patients treated intensively developed high NAP scores. Elective splenectomy performed during the chronic phase of CGL is followed by a pronounced but transient neutrophilia and a concurrent striking rise in the NAP score. Similar changes were observed in patients without CGL who underwent splenectomy. These observations can be explained by assuming that newly formed neutrophils in CGL have a normal content of NAP but are rapidly sequestered in non-circulating extramedullary pools, whereas the circulating neutrophil with a typically low NAP content is a relatively aged cell which has lost enzyme activity. In subjects with or without CGL, removal of the spleen, a major site of such pooling, temporarily permits the circulation of newly formed neutrophils but eventually other organs assume the sequestering functions of the spleen. Thus the aberrations of NAP score seen in CGL might be attributable not to an intrinsic cellular defect but to an exaggeration of the granulocyte storage phenomena which also occur in subjects without CGL.

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Section: Effects Of Splenectomy Upon Nap Scorementioning

confidence: 99%

Neutrophil alkaline phosphatase score in chronic granulocytic leukaemia: effects of splenectomy and antileukaemic drugs.

Spiers¹,

Liew²,

Baikie³

1975

J Clin Pathol

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“…Fluorescent staining was carried out using a modification of a previously de scribed method, which has been shown to give a more exact identification of the Y chromosome [16].…”

Section: Methodsmentioning

confidence: 99%

Absence of the Y Chromosome in Patients with Chronic Granulocytic Leukaemia

Whittaker¹,

Davies²,

Khurshid³

1975

Acta Haematol

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“…From the place of discovery, the karyotype marker was given the name Philadelphia (Ph) chromosome. Chromosome banding techniques identi®ed Ph as resulting from a deleted chromosome 22 (Caspersson et al 1970;O'Riordan et al 1971). Using the same techniques, Rowley (1973) reported that the Ph chromosome is the result of a translocation involving chromosomes 9 and 22.…”

Section: The Philadelphia (Ph) Chromosomementioning

confidence: 99%

Chronic myelogenous leukemia: molecular and cellular aspects

Pasternak

Hochhaus

Schultheis

et al. 1998

Journal of Cancer Research and Clinical Oncology

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Chronic myelogenous leukemia (CML) originates in a pluripotent hematopoietic stem cell of the bone marrow and is characterized by greatly increased numbers of granulocytes in the blood. Myeloid and other hematopoietic cell lineages are involved in the process of clonal proliferation and differentiation. After a period of 4-6 years the disease progresses to acute-stage leukemia. On the cellular level, CML is associated with a specific chromosome abnormality, the t(9; 22) reciprocal translocation that forms the Philadelphia (Ph) chromosome. The Ph chromosome is the result of a molecular rearrangement between the c-ABL proto-oncogene on chromosome 9 and the BCR (breakpoint cluster region) gene on chromosome 22. Most of ABL is linked with a truncated BCR. The BCR/ABL fusion gene codes for an 8-kb mRNA and a novel 210-kDa protein which has higher and aberrant tyrosine kinase activity than the normal c-ABL-coded counterpart. Phosphorylation of a number of substrates such as GAP, GRB-2, SHC, FES, CRKL, and paxillin is considered a decisive step in transformation. An etiological connection between BCR/ABL and leukemia is indicated by the observation that transgenic mice bearing a BCR/ABL DNA construct develop leukemia of B, T, and myeloid cell origin. CML cells proliferate and expand in an almost unlimited manner. Adhesion defects in bone marrow stromal cells have been proposed to explain the increased number of leukemic cells in the peripheral blood. However, findings of our laboratory have shown that the BCR/ABL chimeric protein that is expressed in transfected cells may, under certain conditions, also increase the adhesion to fibronectin via enhanced expression of integrin. Our previous immunocytological studies on the expression of beta1 and beta2 integrins have found no qualitative differences between normal and CML hematopoietic cells in vitro. Even long-term-cultured CML bone marrow or blood cells continuously express those adhesion molecules that are characteristic of the cytological type. Recent experiments indicate that certain early CML progenitors may adhere to the stromal layer in vitro similarly to their normal counterparts. They cannot be completely removed by long-term culture on allogeneic stromal cells. At present, the only curative therapy is transplantation of allogeneic hematopoietic stem cells. Based on the molecular and cellular state of knowledge of CML, new therapies are being developed. BCR/ABL antisense oligonucleotides, inhibitors of tyrosine kinase, peptide-specific adoptive immunotherapy or peptide vaccination, and restoration of hematopoiesis by autologous stem cell transplantation following CML cell purging are examples of important approaches to improving CML treatment.

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Distinguishing between the Chromosomes involved in Down's Syndrome (Trisomy 21) and Chronic Myeloid Leukaemia (Ph1) by Fluorescence

Cited by 124 publications

References 8 publications

Neutrophil alkaline phosphatase score in chronic granulocytic leukaemia: effects of splenectomy and antileukaemic drugs.

Neutrophil alkaline phosphatase score in chronic granulocytic leukaemia: effects of splenectomy and antileukaemic drugs.

Absence of the Y Chromosome in Patients with Chronic Granulocytic Leukaemia

Chronic myelogenous leukemia: molecular and cellular aspects

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