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At least 19 recordsLinked to original sources
PubMed1978

Studies on the specificity of CML. Report from a CML-workshop.

In a collaboratory study involving eight different laboratories 30 human, mixed lymphocyte culture educated cytotoxic lymphocytes (CTLs) were identified yielding reproducible cytolysis on allogenic lymphocyte target cells without detectable HLA-A, B (and C) antigenic sharing between stimulator and target cells. These CTLs were collected in one laboratory (Aarhus) and tested in parallel against a population sample of 100 unrelated, healthy Danes. The testing was only performed once and 11 CTLs did not discriminate in the population, probably due to transportation damage. On the basis of pairwise comparisons between 19 CTLs, three tentative CML-defined specificities could be recognized. These three groups may have defined monospecific traits of allelic genetic origin as judged by a mutually negative, albeit not significant, correlation and a fit to Hardy-Weinberg equilibrium. The concept of determinants other than the serologically defined HLA antigens recognized by some CTLs can thus still be maintained as can the approach to CML typing tested in this workshop.

Computers↗
PubMed1979

The chromosomes and causation of human cancer and leukemia: XXXVIII. Cytogenetic experience in Ph1-negative chronic myelocytic leukemia (CML).

Among 300 patients with chronic myelocytic leukemia (CML) followed at our institute during the last ten years, 36 (12%) were thought to have Ph1-negative CML. In eight of these patients, chromosomal abnormalities were found in the leukemic cells; in four, the karyotypic abnormalities were established with banding techniques. The data of the present study and a review of the literature regarding chromosomal changes in Ph1-negative CML indicate that: 1) no characteristic or consistent karyotypic change is present in Ph1-negative CML and that diploidy is more common in this than any other leukemia; 2) the most common changes involve group C chromosomes (particularly +8); and 3) a missing Y is less common in Ph1-negative CML than in its Ph1-positive counterpart. The karyotypic changes in Ph1-negative CML resemble more those encountered in Ph1-positive CML than in acute myeloblastic leukemia (AML). The much shorter survival of the Ph1-negative CML patients vs that of the Ph1-positive group was again substantiated, and some of the previously reported clinical and laboratory findings unique to Ph1-negative CML were confirmed. On the basis of the cytogenetic findings it is concluded that Ph1-negative CML appears to be an entity unto itself.

Adult↗
PubMed1977

Regulatory mechanisms in cell-mediated immune responses. II. Comparison of culture-induced and alloantigen-induced suppressor cells in MLR and CML.

Two antigen-nonspecific T cell-dependent suppressor systems were compared for their effects upon CML and MLR. Suppressor cells generated by an in vitro culture of spleen cells were compared with suppressor cells generated by in vivo priming with alloantigen. Culture-induced suppressor cells were themselves unable to respond in CML or MLR; were able to suppress actively the CML and MLR responses of untreated responding cells; were mitomycin-sensitive; and, produced no easily demonstrable suppressive supernatant. Alloantigen-primed cells were able to respond in CML and LR; could suppress proliferation in MLR, but were able to suppress CML only after mitomycin treatment; and, produced suppressive supernatants active in suppressing both CML and MLR. In addition to cataloging the differences and similarities between these suppressor populations, the data have been employed to analyze the mechanisms by which suppression occurs in CML and MLR.

Animals↗
PubMed1978

Cytogenetic "staging" of chronic myeloid leukemia (CML).

Establishment of the exact chromosome constitution in the leukemic cells of CML can serve as a mean of "staging" of the disease. Such "staging" is of more than theoretical value, for it may be utilized not only in the differentiation of the type of CML present, but may also serve as a useful guide in the therapy of the disease. The most important determination is to ascertain whether the CML is Ph1 positive or negative, for the latter form of the disease has a much poorer prognosis and requires a different therapeutic approach than the Ph1-positive disease. A system of "staging" of Ph1-positive CML is proposed, allowing a clear understanding of the type of therapy to be used and the results that can be expected from such therapy. The presence or absence of chromosomally normal cells plays a crucial role in this respect and points to the importance of diagnosing CML in its very early stages, when normal cells are usually present and leading to a much more favourable prognosis. The possible role of a missing Y in the leukemic cells and Ph1-translocations other than the standard one in the prognosis and clinical picture of CML is discussed.

Chromosome Aberrations↗
PubMed1979

Chronic myelocytic leukemia (CML): failure to detect residual normal committed stem cells in vitro.

Granulocytic colonies grown in culture from marrow and peripheral blood from five patients with Ph1-positive CML and heterozygous at the G-6-PD locus were analyzed for G-6-PD in order to identify CFU-C that do not arise from the CML clone. The patients had both B and A enzymes in normal tissues, but their CML clones typed as B. Whereas about 50% of colonies from normal subjects heterozygous as the G-6-PD locus show type-A G-6-PD and 50% type B, only two of the 1308 colonies from the CML patients had type-A G-6-PD. These data provide little evidence for persistence of normal committed stem cells in CML, a finding in contrast to that made previously in polycythemia vera, another clonal stem cell myeloproliferative disorder.

Adult↗
PubMed1976

Augmentation of cell mediated lysis (CML) by THF.

The in-vitro model of cell mediated lysis (CML) was used to study whether a thymic hormone (THF) participates in the processes which lead to generation of effector cells. It was found that THF increases the capacity of effector cells from spleens of intact mice in the CML assay. This effect of THF on generation of effector cells was manifested when THF was present during the mixed lymphocyte culture. On the other hand, addition of THF to the effector (CML) phase did not elevate the lytic capacity of killer cells. Moreover, THF compensated the impaired lytic capacity of effector cells from adult thymectomized mice and raised it to the level of intact mice. The results are compatible with the hypothesis that THF acts on the generation of CML effector cells of both intact and adult thymectomized mice.

Animals↗
PubMed1976

Human lymphocyte subpopulations involved in MLC and CML.

Lymphocyte subpopulations from human peripheral blood were tested for their capacity to stimulate allogenic cells in MLC and for their ability to develop into cytotoxic cells in cell-mediated lympholysis (CML). By various cell separation experiments lymphocyte suspensions were depleted or enriched with respect to Fc receptor-bearing cells (detected as EA-RFC) and Ig-bearing cells. It was concluded that Fc receptor-bearing cells and Ig-bearing cells belong to different subpopulations. Furthermore, about 30% of the Fc receptor-bearing cells had T cell characteristics. The MLC stimulatory capacity was mainly confined to the Ig-bearing lymphocytes, and the Fc receptor-bearing cells and T cells exerted very little stimulation. Removal of Fc receptor-bearing cells strongly decreased the development of cytotoxic lymphocytes in CML. However, removal of Fc receptor bearing cells after MLC activation no longer affected cytotoxicity in CML. The activity in antibody-dependent lymphocytotoxicity was strongly decreased when Fc receptor-bearing cells were removed either before or after MLC activation. It was concluded that the cytotoxic precursor cells in CML bear an Fc receptor, which is either lost or blocked during MLC activation.

Binding Sites↗
PubMed1976

Correlation of graft-versus-host mortality and positive CML assay in the mouse.

GVH mortality was encountered in each of six parental-F1 hybrid combinations with antigenic disparity sufficient to cause strong positive CML. Mortality was encountered in only one of nine combinations in which CML is negative (or weak). The CML assay may thus be useful, but is not perfect, in prediction of GVH mortality. Of the eight CML-negative, GVH nonlethal combinations, three were MLC positive and also activated donor T-cell proliferation in vivo.

Animals↗
PubMed1978

Chromosome analysis of spleen and/or lymph nodes of patients with chronic myeloid leukemia (CML).

Origin and spread of the chromosomally abnormal cells that appear in chronic myeloid leukemia (CML) after transformation are unknown. Spleen and lymph node may be involved. In 16 patients with CML splenectomy and/or adenectomy were performed before or during the blastic crisis of the disease, followed by a chromosomal analysis of the cells from the removed organ. At the same time, the chromosomes of the blood cell and of the bone marrow were also analyzed. Analyses were done with R banding. The results show that an extramedullary clonal development with duplication of the Ph1 chromosome and other features occurred. From a cytogenetic standpoint, acute blastic phase of CML is frequently characterized by an increased number of chromosomes owing to preferential gain of additional chromosomes. This, then, would clearly point to extamedullary acute transition in CML.

Bone Marrow↗
PubMed1976

The chromosomes and causation of human cancer and leukemia. XVIII. The missing Y in acute myeloblastic leukemia (AML) and Ph1-positive chronic myelocytic leukemia (CML).

The occurrence of a missing Y chromosome was investigated in the bone marrow cells of male individuals, i.e., 255 controls, 73 with acute myelocytic leukemia (AML) and 59 with Ph1-positive chronic myelocytic leukemia (CML). The incidence in controls of individuals with 45,X cells increased with age, particularly after the age of 60. In AML, 45,X metaphases were detected in two patients over 70 years of age, but the leukemia seemed to have involved the 46,XY cells rather than the 45,X cells. Four of the six patients with No. 8-No. 21 translocation and two of the 16 with major karyotypic abnormalities (MAKA) exhibited a missing Y in the leukemic cells in addition to other karyotypic aberrations. Four of the Ph1-positive CML patients exhibited a missing Y in all or nearly all the cells in the bone marrow along with the Ph1. In one patient, additional chromosome abnormalities involved the 46,XY,Ph1 rather than the 45,X,Ph1 cells. The genesis of the missing Y in CML cells may be related to the presence of the Ph1, though apparently the patient's age also plays a role. It is our hypothesis that 45,X or 45,X,Ph1 cells are resistant to the development of further chromosomal abnormalities and, thus, reflect their resistance to being involved in an acute leukemic process.

Adolescent↗
PubMed1976

[Vitamin B12 metabolism of human granulocytes. Differences in vitamin B12 uptake of normal granulocytes and CML leukocytes].

The total cell B12 level in chronic myelocytic leukaemia (CML) is low. The uptake of 57Co-cyanocobalamin by normal granulocytes, lymphocytes and CML leukocytes was studied. It was found that the uptake of vitamin B12 was dependent on its concentration. The velocity of the uptake by CML leukocytes was decreased. The reaction showed a non-competitive inhibition. Lymphocytes had the lowest uptake. Na2EDTA inhibited the vitamin B12 uptake of normal granulocytes.

Cobalt Radioisotopes↗
PubMed1976

Blast crisis of chronic myeloid leukaemia (CML). II. Cell surface marker analysis of "lymphoid" and myeloid cases.

Fourteen cases of philadelphia chromosome (Ph1) positive chronic myeloid leukaemia in blast transformation have been investigated using cell surface markers. Morphologically eight cases were lymphoid and the remainder myeloid in appearance. All cases were negative with surface markers for thymocytes and T and B lymphocytes. Five of the lymphoid cases reacted with an antiserum specific for acute lymphoid leukaemia )ALL) of non-T non-B type and were also weakly reactive with a lymphocyte reactive antiserum. A sixth patient, whose blast cells were anti-ALL negative (ALL-) at presentation, subsequently developed central nervous system leukaemia with anti-ALL positive (ALL+) blast cells in the CSF. In all cases the leukaemic blast cells showed greatly diminished expression of cholera toxin receptors when compared to granulocytic cells from the chronic phase of CML. This parallels weak or negligible expression of the cholera toxin receptor in ALL and AML. These results suggest that the blastic phase of CML may involve different cellular derivatives of a pluripotential stem cell in which the primary malignant/genetic changes reside. The blast crisis of CML can therefore be heterogeneous with respect to cellular expression and in a significant proportion of patients involves a cell which is by membrane markers and morphological criteria indistinguishable from that seen in the common form of ALL. In these cases the Philadelphia chromosome may be the only distinguishing cellular characteristic.

Cell Transformation, Neoplastic↗
PubMed2025

Aberrant expression of MAPK1 and MCTS1 in chronic myeloid leukemia (CML).

Genomic amplification may result in aberrant gene expression and support development of cancer, including chronic myeloid leukemia (CML). In CML cell line K-562, we recently reported overexpression of TBX1 located at chromosomal position 22q11, focally co-amplified together with BCR, part of the CML hallmark fusion gene BCR::ABL1. Here, we extended that study, by identifying genomically amplified and overexpressed MAPK1/ERK2 at 22q11 together with MCTS1 at Xq22. Using pharmacological inhibitors and siRNA-mediated knockdown assays, our data collectively revealed novel regulatory connections between TBX1, MAPK1 and MCTS1, which may play a role in drug resistance.

Journal Article↗
PubMed1979

Abnormalities in the erythroid progenitor compartments in patients with chronic myelogenous leukemia (CML).

Peripheral blood and bone marrow specimens from 6 patients with Ph1-positive CML were evaluated for their content of erythropoietic and granulopoietic colony-forming progenitor cells. Specimens obtained from untreated patients showed marked increases in all compartments the most dramatic of which were for CFU-E and circulating CFU-C. This increased cell flow down the early stages of the red cell pathway in CML suggests that heightened proliferation and differentiation of primitive hemopoietic cells may be a more general phenomenon than previously suspected in this disease. In 5 of 6 patients, abnormal erythroid progenitors capable of proliferation and differentiation into hemoglobinized erythroblasts in cultures containing less than 0.002 units of erythropoietin/ml were regularly detected. In the 6th patient abnormal growth was not seen in cultures of the initial marrow obtained but was detected in cultures set up with peripheral blood taken 7 months later. The unexplained amplification of the erythropoietic compartment and the ability of some of these cells to mature in vitro in the virtual absence of erythropoietin is at variance with the anemia characteristic of untreated patients. This suggests the possibility of a major differentiation block at the level of CFU-E. Further studies of the properties of erythroid progenitors in these patients should help to provide new insights into the pathogenesis of CML and may provide useful markers for monitoring engrafted cell function after autotransplantation of patients in blast crisis.

Adult↗
PubMed1977

Relationship between trinitrophenyl and H-2 antigens on trinitrophenyl-modified spleen cells. II. Correlation between derivatization of H-2 antigens with trinitrophenyl and the ability of trinitrophenyl-modified cells to react functionally to the CML assay.

Spleen cells were modified with varying concentrations of trinitrobenzene sulfonic acid and then assayed for both their ability to stimulate syngeneic spleen cells into displaying a cytotoxic effect against TNP-modified target cells and for the extent of TNP derivatization of H-2 antigens. It was found that there was a direct correlation between the extent of derivatization of H-2 antigens and the ability of such derivatized cells to act as stimulator cells in the TNP-CML assay. Thus, these data lend support to the altered self or interaction antigen hypothesis as the explanation for the H-2 gene restriction of syngeneic CML. Target cells were also modified with TNBS at varying concentrations to determine the optimal concentration required to permit lysis in the CML assay. The results of these experiments indicate that similar concentration ranges of TNBS are required to create antigenic determinants on the target cells as well as immunogenic determinants on the stimulator cells that can be recognized by cytotoxic T cells.

Animals↗