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Biomedical subjects

L C Chan

Publications and source records attributed to L C Chan.

190 records · Page 11Linked to original sources
PubMed1986

Lineage promiscuity in hemopoietic differentiation and leukemia.

An increasing number of reports document instances in which individual leukemic cells coexpress markers normally believed to be restricted to a single lineage. This has been interpreted by McCulloch and colleagues as aberrant programming or lineage infidelity and contrasts with earlier suggestions that lineage fidelity of gene expression was usually maintained in leukemia. We argue that several examples of infidelity are suspect on technical grounds, whereas others are bona fide and require explanation, eg, partial rearrangements and expression of Ig heavy-chain and/or T cell receptor genes in inappropriate cells and terminal deoxynucleotidyl transferase in leukemic myeloblasts. Individual examples of truly aberrant gene expression may well occur in leukemia but with insufficient regularity to be of general significance. We suggest that verifiable and consistent examples of apparent lineage infidelity do not reflect genetic misprogramming but rather the existence of a transient phase of limited promiscuity of gene expression occurring in normal biopotential or multipotential progenitors and able to be preserved as a relic in leukemic blast cell populations that are in maturation arrest. This alternative explanation has interesting implications for mechanisms of hematopoietic differentiation and leads to some testable predictions.

Animals↗
PubMed1985

Contribution of immunophenotype to the classification and differential diagnosis of acute leukaemia.

The diagnostic value of a panel of monoclonal antibodies was assessed in 100 consecutive patients with acute leukaemia. 97 patients were clearly phenotyped. Clinical and haematological feedback showed that the immunological data made a critical contribution to the final haematological diagnosis in 19 patients and provided useful confirmatory data in another 78. Immunophenotype also provided the basis for a subset classification of known prognostic relevance to acute lymphoblastic leukaemia (ALL). Immunophenotype and haematological findings conflicted in 2 cases, and 3 cases were unclassifiable with the antibody panel. In these difficult cases leukaemic-cell DNA was investigated for immunoglobulin gene rearrangement. Immunophenotyping with selective probes may be used in conjunction with other laboratory analyses (eg, karyotyping) in the routine investigation of patients with acute leukaemia.

Acute Disease↗
PubMed1985

Acute biphenotypic leukaemia (myeloid and null-ALL type) supervening in a myelodysplastic syndrome.

An acute leukaemia was seen in a 72-year-old patient with a myelodysplastic syndrome (MDS) of 14 months duration, who had been treated only with steroids. The morphological appearance of the blast cells suggested a poorly differentiated cell type. Surface marker analysis, including double staining studies, showed the coexistence of a population of null acute lymphoblastic leukaemia (ALL) blast cells together with acute myeloid leukaemia type cells. No chromosomal alterations were detected. The change from a chronic MDS to an acute leukaemia of mixed (myeloid and null ALL) type suggests either transformation of a pre-existing abnormal clone or de novo appearance of two separate leukaemic clones.

Aged↗
PubMed1985

Monosomy 7 and multipotential stem cell transformation.

Monosomy 7 was the sole karyotypic abnormality seen in a case of biphenotypic leukaemia involving both the myeloid and lymphoid lineages and in a case of de novo ALL undergoing a phenotypic shift to acute myeloid leukaemia at relapse. These observations suggest that monosomy 7 can be associated with transformation of a common lymphoid-myeloid progenitor cell.

Aged↗
PubMed1985

Reactivity of rat monoclonal antibody CAMPATH-1 with human leukaemia cells and its possible application for autologous bone marrow transplantation.

The rat monoclonal antibody CAMPATH-1 recognizes a hitherto undefined antigen present on virtually all normal lymphocytes and monocytes. Its reactivity with 105 samples of fresh leukaemic cells and 13 cell lines was measured by indirect fluorescence and peroxidase staining to define in more detail which stages of differentiation it recognizes. It was found to bind to cells from virtually all cases of lymphoid leukaemia (B cell CLL, T cell ALL, cALL and the few examples of HCL, PLL, Sezary syndrome and CGL in lymphoid blast crisis). The single case of cALL in relapse and four of six cases of null ALL were negative. Binding to non-lymphoid leukaemia cells (AML, AMML, AMoL, APL, AEL and CGL in blast crisis) was weaker or undetectable. Binding to established lymphoid cell lines was generally weak compared with fresh cells but some lines (MOLT4, DAUDI and X308) expressed adequate amounts of antigen to be lysed by CAMPATH-1 with human complement. Because CAMPATH-1 is very effective at killing lymphocytes in the presence of human complement, it has been used for removal of T cells in allogeneic transplants. The present results suggest that it might also have a role in purging bone marrow of leukaemia cells prior to autologous transplantation for acute lymphocytic leukaemia.

Animals↗
PubMed1979

The extraction and analysis of lipopolysaccharides from Pseudomonas aeruginosa strain PAO, and three rough mutants.

Three spontaneously arising rough mutants of Pseudomonas aeruginosa have been isolated by selection for resistance to virulent lipopolysaccharide (LPS) specific bacteriophages. In addition, the first phages specific for rough mutants of P. aeruginosa were isolated. Using these phage and autoagglutination patterns in 4% NaCl and acriflavine, these mutants could be clearly distinguished from the wild-type strain and each other. Chemical analysis of the LPS together with chromatographic resolution of the polysaccharide moieties showed alterations in both O-specific side chains and core regions.

Chemical Phenomena↗
PubMedDate not supplied

A novel abl protein expressed in Philadelphia chromosome positive acute lymphoblastic leukaemia.

The Philadelphia (Ph) chromosome breakpoints in chronic myelocytic leukaemia are clustered on chromosome 22 band q11 in a 5.8-kilobase (kb) region designated bcr. The c-abl protooncogene is translocated from chromosome 9 band q34 into bcr and the biochemical consequence of this molecular rearrangement is the production of an abnormal fusion protein bcr-abl p210 with enhanced protein-tyrosine kinase activity compared to the normal p145 c-abl protein. The Ph chromosome translocation is also seen in some acute lymphoblastic leukaemias with B-cell precursor phenotypes some of which have bcr rearrangement (bcr+) and some do not (bcr-). We present evidence that the Ph+, bcr- leukaemias are associated with a novel p190 abl kinase. We propose that acute lymphoblastic leukaemias that are bcr+, p210+ are probably lymphoid blast crises following a clinically silent chronic phase of chronic myelocytic leukaemia arising in multipotential stem cells whereas bcr-, p190+ cases are de novo acute lymphoblastic leukaemias arising in more restricted precursors.

Adolescent↗