Myelocytic Leukemia In Blast Crisis Research Articles

High serum levels of soluble interleukin-2 receptor in acute myeloid leukemia: Correlation with poor prognosis and CD4 expression on blast cells

Backgorund: Although increased serum levels of soluble interleukin-2 receptor (sIL-2R) and their clinical importance are well known in mature type lymphoproliferative disorders (LD), little data is available about such information in acute type hematological malignancies. Methods: We examined the serum levels of sIL-2R in 57 adult patients with acute type leukemias: 32 with acute myeloid leukemia (AML), 14 acute lymphoblastic leukemia (ALL) and 11 chronic myelocytic leukemia in blast crisis (CMLBC), and in 29 adult patients with mature type LD, and assessed their cellular and clinical relevance in acute type leukemias. Results: No significant differences were seen in the sIL-2R levels between acute type leukemias and mature type LD. In AML, serum sIL-2R levels were related to the cell surface CD4 expression on blast cells, and patients with higher levels ≧2000U/ml had a poorer prognosis (lower response to chemotherapy and shorter overall survival). Conclusions: These results suggest that serum sIL-2R level elevates in acute type leukemias like mature type LD, and increased sIL-2R levels in adult AML are correlated with certain biological and clinical characteristics.

Expression of the Fas/APO-1/CD95 antigen mediating apoptosis in human leukemic cells

The Fas/APO-1 antigen is not detected on peripheral blood leukocytes of patients with chronic myelocytic leukemia in the chronic phase, but is expressed on blast cells in 50% of patients with chronic myelocytic leukemia in blast crisis. The expression of Fas/APO-1 correlates with that of leukocytic CD34 antigen. In patients with lymphomas, acute lymphoblastic leukemia, or acute myeloblastic leukemia some tumor cells carry Fas/APO-1 antigen.

Severe Hypercalcemia in a Child with Relapsed Megakaryoblastic Leukemia: Report of a Case and Review of the Literature

Severe Hypercalcemia in a Child with Relapsed Megakaryoblastic Leukemia: Report of a Case and Review of the Literature

Prognostic significance of the blast self-renewal capacity in patients with acute myeloid leukemia

The proliferation of leukemic cells in acute myeloid leukemia (AML) is supported by a small subpopulation of leukemic blast progenitors, which can be detected in methylcellulose and suspension cultures. It is important to determine the association between the biologic properties of leukemic blast progenitors and the clinical prognosis of patients with AML. Ninety-five patients with AML and two patients with chronic myelocytic leukemia in blast crisis were studied. T-cell depleted mononuclear cells obtained from the peripheral blood cells were cultured in both methylcellulose and suspension cultures. In methylcellulose culture, primary blast colony formation (PE1) and secondary blast colony formation (PE2) were enumerated. The recovery of clonogenic cells was determined in suspension culture. The association between PE1, PE2, or clonogenic cell recovery in suspension and the remission induction outcome or survival duration of the patients were examined. PE1 was not associated with the remission induction outcome. PE2 and clonogenic cells recovered in suspension were significantly associated with the remission induction. Furthermore, the survival duration of the patients who achieved complete remission was associated significantly with the number of clonogenic cells recovered in suspension. PE1 reflects the terminal divisions of leukemic blast progenitors, whereas PE2 and the recovery of clonogenic cells in suspension culture are considered to reflect the self-renewal of leukemic blast progenitors. The results suggest that the self-renewal capacity of leukemic blast progenitors is predictive of not only remission induction outcome but also survival duration of patients with AML.

Genotypic and cytogenetic study of acute myelocytic leukemia and chronic myelocytic leukemia in blast crisis: Specific δ rearrangement pattern does not involve J δ gene locus

We have analysed the configuration of immunoassociated genes and the karyotypes of 30 patients with acute myelocytic leukemia (AML) and 10 with chronic myelocytic leukemia in blast crisis (CML-BC). In AML, the frequencies of T-cell receptor (TcR) β, γ, and δ chain and immunoglubulin heavy and light chain gene rearrangements were 4.2%, 19%, 8%, 10.7% and 10.5%, respectively. In CML-BC, they were 10%, 20%, 40%, 50% and 0%, respectively. Nine patients had abnormalities in chromosome 2, 7 or 14, upon which immunoassociated genes are located. There seems to be no apparent relationship between these chromosome abnormalities and gene rearrangements. In all patients but one (5/6), the δ rearrangement was accompanied by other immunoassociated gene rearrangements. Molecular size analysis revealed specific δ rearranged band(s) (19.5 kb-BamHI and/or 6.9 kb-EcoRI), as commonly detected in B-acute lymphocytic leukemia (ALL). All the patients with the δ rearranged band, however, had a germline configuration of J δ gene loci, suggesting a DD or V(D)D (probably V δ2(D)D) pattern. This study also indicates that the δ rearrangement is specific in AML or CML-BC and distinct from that in early T leukemia/lymphoma.

Myeloid leukemia differentiation by phorbol ester and retinoic acid: A practical approach

The effects of TPA (12-0-tetradecanoylphorbol-13-acetate) and RA (retinoic acid) were investigated on the cell lines HL60 (acute promyelocytic leukemia) and K562 (erythroleukemia) and on cells from patients with several kinds of leukemia. There were 14 cases of acute lymphocytic leukemia (ALL), 2 cases of chronic lymphocytic leukemia (CLL), 23 cases of acute myeloid leukemia (M1-M7), 5 cases of chronic myelocytic leukemia in blast crisis (CML-BC) and 2 mixed leukemias. In almost all of the cases examined, after TPA exposure cells from patients with proven myeloid leukemia became adherent to the substrate, while lymphoid leukemia cells remained in suspension, allowing the differentiation of lymphoid from myeloid blasts. The only exception was in one case of CLL, which had cells that became adherent with long filamental projections. In addition, increased phagocytosis following TPA exposure permitted characterization of M7 as this was the only myeloid leukemia negative for phagocytosis. Further discrimination between the subtypes of myeloid leukemia could be based on the increased lysozyme production seen after TPA in M4 and M5. Esterase positivity allowed the discrimination of M1 cells, which were negative before and after TPA treatment. In agreement with the results of other authors, TPA and RA led to independent ways of differentiation, granulocytic-like lineage and monocytic-like cells being favored by RA and TPA, respectively. The capacity of the same cell to differentiate into more than one lineage, depending on whether RA or TPA was used, was only seen in the present study with M3 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

A phase II study of diaziquone in childhood leukemia: a report from the Children's Cancer Study Group.

Diaziquone (aziridinylbenzoquinone, AZQ) was given by 30-min infusion at 25 mg/m2/day on a daily x 5 schedule to 16 children with acute lymphoblastic leukemia (ALL) in bone marrow relapse, 16 children with acute nonlymphocytic leukemia (ANLL) in bone marrow relapse, and 1 child with chronic myelocytic leukemia in blast crisis. None of the children achieved bone marrow remission. Five children (four with ALL and one with ANLL) were also evaluable for the response of central nervous system leukemia; all had a significant reduction in the cerebrospinal fluid blast count. Mild transient transaminase elevation was commonly seen. Grade 3 and 4 hyperbilirubinemia was seen in association with sepsis. AZQ was ineffective for induction of bone marrow remission as utilized in this study.

Distinct human leukemia-associated cell surface glycoprotein GP160 defined by monoclonal antibody SN6.

In this study, a monoclonal antibody (mAb) termed SN6 was generated by immunizing a mouse with a non-T-cell leukemia antigen preparation isolated from cell membranes of leukemia cells derived from a patient (FJ) with non-T/non-B-cell-type acute lymphoblastic leukemia (ALL). SN6 was tested against a variety of cultured and uncultured human cell specimens by using a sensitive cellular radioimmunoassay. Among the 26 cultured malignant and nonmalignant cell lines tested, SN6 reacted with all of the 6 leukemic non-T/non-B (including pre-B)-cell lines tested--i.e., KM-3, NALM-16, REH, NALL-1, NALM-1, and NALM-6. Of these cell lines, 5 were derived from individual patients with ALL; the remaining 1 was from a patient with chronic myelocytic leukemia in blast crisis. In addition, SN6 reacted with 3 of 3 leukemic myelo-monocytic cell lines tested--i.e., ML-2, HL-60, and U937. SN6 did not react with any other cell lines. A consistent result was obtained with 42 fresh (uncultured) cell specimens derived from individual patients with several different types of leukemias. SN6 reacted with 11 of 16 non-T/non-B (including pre-B)-cell ALL specimens. In addition, it reacted with various myelo-monocytic leukemia cell specimens to various degrees. SN6 did not show a significant reaction with normal peripheral blood cells tested, which included B cells, T cells, granulocytes, monocytes, and erythrocytes. However, it reacted with a small population (approximately 1% as determined by immunofluorescence staining) of normal bone marrow cells. The approximate molecular mass of the glycoprotein antigen defined by SN6 was determined to be 160,000 by radioimmunoprecipitation followed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. Only one component of 80,000 daltons was formed upon reduction of the 160,000 molecular mass antigen. Therefore, this antigen is apparently a homodimer of a 80,000-dalton subunit. This conclusion was further corroborated by two-dimensional gel analysis, which showed a single well-defined spot for the reduced antigen. We designate this distinct human leukemia-associated cell surface antigen "GP160."

A lymphoblastoid cell line with high phagocytic activity established from peripheral blood of a patient with chronic myelocytic leukemia in blast crisis.

A human hematopoietic cell line (K-23-M) was established from a patient with chronic myelocytic leukemia in blast crisis. Morphologically, the cultured cells were lymphoblastoid cells that produced IgA and were Epstein-Barr viral nuclear antigen positive. But they showed high phagocytic activity to glutaraldehyde-treated sheep red cells and had properties of a monocyte or macrophage that included surface Fc receptors, alpha-naphthyl butyrate esterase positivity blocked by NaF, migration in soft agar and the ability to attach to a glass surface. Lysozyme secretion was absent, and chromosomes were diploid and Ph1 negative. This cell line is unique in that it has strong phagocytic activity. Its existence shows that lymphoblastoid cell line may be a more important cell line for the study of human hematopoietic cells than previously has been believed.

Ultrastructural characterization of de novo and secondary leukemias.

Cells from 95 patients with acute leukemia were studied by cytochemistry, light microscopy, and transmission electron microscopy (TEM), and were classified according to the French-American-British (FAB) guidelines. This group included 63 patients with acute nonlymphocytic leukemia (ANLL) de novo, 18 with acute lymphocytic leukemia (ALL), and 14 with ANLL as a second malignancy. In addition, 13 cases of chronic myelocytic leukemia in blast crisis were studied. Ultrastructural examination resulted in reclassification of 6 cases of ANLL de novo; two of these were reclassified from M2 (myeloblastic leukemia with maturation) to M3 variant (microgranular variant of hypergranular promyelocytic leukemia). The classification of the cases of CML in blast crisis was identical by light microscopy and TEM. IN 1 case of myeloblastic crisis, however, basophilic granules were demonstrated by TEM but were not appreciated by light microscopy. Classification of the cases of secondary leukemia was possible by light microscopy and cytochemistry in all 14 cases, but was often difficult since the cytochemical reactions were usually less intense than in de novo ANLL. This was particularly true in those cases classified as M1, and in such cases, TEM was required to confirm the diagnosis.

Studies on the ability of monoclonal antibodies to selectively mediate complement-dependent cytotoxicity of human myelogenous leukemia blast cells.

A panel of monoclonal antibodies that bind to leukemic blast cells from patients with acute myelocytic leukemia and chronic myelocytic leukemia in blast crisis was studied for their ability to mediate complement-dependent lysis of a variety of cell populations from patients with leukemia, normal blood cells, and human leukemia cell lines. Several of these monoclonal antibodies were selectively cytotoxic to myeloid leukemia cells (AML-1-99, AML-1-211, AML-2-30, CML-75, CML-115, and CML-150). Although they were all capable of binding to normal cell populations, none of these hybridomas were cytotoxic to normal cells. Three of these antibodies (AML-1-211. CML-75, and CML-150) were cytotoxic to some leukemia cell samples only after dilution of the hybridoma supernatant, i.e., they showed a prozone. Binding of these three antibodies, as well as another, AML-1-201, as determined in a radioimmunoassay, also showed a prozone. Other monoclonal antibodies are described (AML-2-23 and AML-2-9) that mediate complement-dependent cytotoxicity to myeloid leukemia cells as well as selected normal cell types (monocytes and lymphocytes, respectively). The potential clinical utility of these monoclonal antibodies is considered in the context of recently encountered problems in the use of monoclonal antibodies to mediate leukemia cell lysis in vivo.

A Case of Chronic Myelocytic Leukemia in Blast Crisis Treated with Allogeneic Bone Marrow Transplantation

A Case of Chronic Myelocytic Leukemia in Blast Crisis Treated with Allogeneic Bone Marrow Transplantation

Expression of common acute lymphoblastic leukemia antigen (CALLA) by lymphomas of B-cell and T-cell lineage

Previous studies have demonstrated that the common acute lymphoblastic leukemia antigen (CALLA) is expressed by leukemic cells from approximately 80% of patients with non-T-cell ALL and 30%-50% of patients with chronic myelocytic leukemia in blast crisis. A small number of normal bone marrow and fetal liver cells also express CALLA, but the functional role of this molecule is unknown. In the present study, we have used a monoclonal antibody (J5) specific for CALLA to study the expression of this antigen in non-Hodgkin's lymphomas. Within the B-cell lymphomas, it was found the CALLA was expressed by almost all Burkitt's and nodular poorly differentiated lymphocytic lymphomas. Within the T-cell lymphomas, CALLA was expressed in 40% of patients with lymphoblastic lymphoma. Three of 3 Burkitt's lymphoma cell lines and three of eight T-lymphoblast cell lines were also found to express CALLA. Normal spleen, lymph node, and thymus cells were not reactive with J5 antibody. These findings indicate that expression of CALLA is not limited to relatively undifferentiated leukemic lymphoblasts but also occurs in more differentiated lymphoid malignancies. However, normal differentiated lymphoid cells in lymph node, spleen, and thymus, which have a phenotype similar to that of lymphoma cells, do not appear to express CALLA.

Expression of Common Acute Lymphoblastic Leukemia Antigen (CALLA) by Lymphomas of B-Cell and T-Cell Lineage

AbstractPrevious studies have demonstrated that the common acute lymphoblastic leukemia antigen (CALLA) is expressed by leukemic cells from approximately 80% of patients with non-T-cell ALL and 30%–50% of patients with chronic myelocytic leukemia in blast crisis. A small number of normal bone marrow and fetal liver cells also express CALLA, but the functional role of this molecule is unknown. In the present study, we have used a monoclonal antibody (J5) specific for CALLA to study the expression of this antigen in non-Hodgkin’s lymphomas. Within the B-cell lymphomas, it was found that CALLA was expressed by almost all Burkitt’s and nodular poorly differentiated lymphocytic lymphomas. Within the T-cell lymphomas. CALLA was expressed in 40% of patients with lymphoblastic lymphoma. Three of 3 Burkitt’s lymphoma cell lines and three of eight T-lymphoblast cell lines were also found to express CALLA. Normal spleen, lymph node, and thymus cells were not reactive with J5 antibody. These findings indicate that expression of CALLA is not limited to relatively undifferentiated leukemic lymphoblasts but also occurs in more differentiated lymphoid malignancies. However, normal differentiated lymphoid cells in lymph node, spleen, and thymus, which have a phenotype similar to that of lymphoma cells, do not appear to express CALLA.

A unique cell surface antigen identifying lymphoid malignancies of B cell origin.

A monoclonal antibody (anti-B1) specific for a unique B cell surface differentiation antigen was used to characterize the malignant cells from patients with leukemias or lymphomas. All tumor cells from patients with lymphomas or chronic lymphocytic leukemias, bearing either monoclonal kappa lambda light chain, expressed the B1 antigen. In contrast, tumor cells from T cell leukemias and lymphomas or acute myeloblastic leukemia were unreactive. Approximately 50% of acute lymphoblastic leukemias (ALL) of non-T origin and 50% of chronic myelocytic leukemia in blast crisis were also anti-B1 reactive. moreover, 21 of 28 patients with the common ALL antigen (CALLA) positive form of ALL were anti-B1 positive, whereas 0 of 13 patients with CALLA negative ALL were reactive. These observations demonstrate that an antigen present on normal B cells is expressed on the vast majority of B cell lymphomas and on approximately 75% of CALLA positive ALL, suggesting that these tumors may share a common B cell lineage.

Purification of terminal deoxynucleotidyltransferase by oligonucleotide affinity chromatography.

Terminal deoxynucleotidyltransferase is an enzyme which has been found to be associated with thymus cells, bone marrow cells, as well as leukocytes from patients with acute lymphoblastic leukemia and chronic myelocytic leukemia in blast crisis. We report here the purification of terminal deoxynucleotidyltransferase by an oligonucleotide affinity (oligo(dT)12-18 cellulose) column. By using a 35 to 70% (NH4)2SO4 cut, Sephacryl S200 column and an oligo(dT) cellulose column, terminal deoxynucleotidyltransferase has been purified from calf thymus cells to a specific activity of more than 8,500 units/mg of protein. The terminal deoxynucleotidyltransferase purified by this method contains no detectable DNA-dependent DNA polymerase or endonuclease activities. Furthermore, sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that the enzyme appears to be homogeneous, with two polypeptides corresponding to the two subunits alpha (10,000) and beta (23,000) of terminal deoxynucleotidyltransferase. These data indicate that oligo(dT)12-18 cellulose can be used as a rapid and selective affinity column for the purification of terminal deoxynucleotidyltransferase.

Autopsy study of blast crisis in patients with chronic granulocytic leukemia, Hiroshima and Nagasaki, 1949-1969.

This report examines the relation of blast crisis to whole body radiation at the time of the atomic bomb (ATB), and describes the autopsy findings in 23 cases of CGL with terminal blast crisis found among 101 CGL cases autopsied in Hiroshima and Nagasaki, Japan, during the period 1949–1969. No evidence was found that blast crisis was more frequent in A-bomb survivors who had been exposed to ionizing radiation ATB than in non-exposed persons. Consequently, in this regard, as in other parameters reported previously, post-irradiation leukemia is shown to be indistinguishable from “spontaneous” leukemia. The occurrence of blast crisis in this series is evaluated in relation to prevalence, year of death, age at onset and death, duration of disease, sex, hemorrhagic manifestations, and leukemic infiltration in various organs.