The karyotype of bone marrow cells in the preleukemic phase of chronic myelocytic leukemia]

The caryotype of bone-marrow cells of 19 patients affected with leukocytosis of obscure origin was examined by means of G-staining. A chronic myelogenous leukaemia in its preleukaemic stage was diagnosed in 11 patients by identifying Ph'-chromosomes in all metaphases observed and a lowered acid leukocyte phosphatase. Besides Ph'-chromosomes an aneuploida (47 chromosomes with trisomia 8) was observed in one patient. The diagnostic and prognostic significance of this pathological caryotype is discussed.     

Multiple myeloma superimposed on chronic myelocytic leukemia

A 65-year-old woman with chronic myelocytic leukemia and multiple myeloma is described. Cases of acute leukemia complicating multiple myeloma have been reported in recent years, but to our knowledge this is the first case where multiple myeloma developed in a patient who had pre-existing chronic myelocytic leukemia.     

Karyotype analysis during development of chronic myelocytic leukemia

We report cytogenetic data concerning 9 patients with chronica granulocytic leukemia and eosinophilia at the onset and during the chronic phase of the disease before the blastic crisis. The cariotype analises in the intermediate phases allowed to determine the first changes which could be involved in the evolutionary events of the disease up to the moment in which the typical markers of the blastic crisis can be found.     

Oncogene activation by chromosomal rearrangement in chronic myelocytic leukemia

A considerable number of human tumors, especially leukemias and lymphomas is associated with a consistent specific chromosome translocation. At a number of the breakpoint regions of these specific aberrations are c-oncogenes (c-onc) located. The structure and/or expression of some of these c-onc is altered as a result of the specific translocation. In the CML-specific (9;22) translocation the transposition of the c-abl oncogene to the chromosome 22 bcr sequences results in the production of a chimeric bcr/c-abl fusion protein. This result strongly suggests that tumor-specific chromosomal aberrations can lead to the activation of cellular oncogenes.     

A phase I/II study of recombinant interferon alpha 2a and hydroxyurea for chronic myelocytic leukemia

Nine previously untreated patients with Philadelphia chromosome-positive chronic myelocytic leukemia (CML) were treated with recombinant interferon alpha 2a (rIFN-alpha 2a) and hydroxyurea. Patients received 6 X 10(6) U rIFN-alpha 2a daily for the first week and 3 X 10(6) U rIFN-alpha 2a daily for the second week. As maintenance treatment starting on day 15, patients received 3 X 10(6) U rIFN-alpha 2a 3 times a week. Simultaneously, hydroxyurea was given, starting at a dose of 40 mg/kg on day one. The maintenance dosage was adjusted to the white blood cell count. Two patients responded with complete hematological remissions but without cytogenetic and molecular-genetic improvements. Seven patients responded with partial hematological remissions. Response to therapy was rapid; normal white blood cell counts were reached after a median of 12 days. The doses of rIFN-alpha 2a and hydroxyurea needed to keep the leucocyte count in the normal range were low (3 X 10(6) U rIFN-alpha 2a 3 times per week, 0.5-1.5 g hydroxyurea/day). Acute toxicity of the combination therapy consisted of fever (9 of 9 patients), flulike symptoms (7 of 9 patients), pruritus and/or rash (3 of 9 patients) and evidence of a tumor cell lysis syndrome (1 of 9 patients). The side effects were not dose-limiting. Combination therapy with rIFN-alpha 2a and hydroxyurea for CML is well tolerated and allows quick and effective hematological control of the disease.     

Abnormal neutrophil myeloperoxidase from a patient with chronic myelocytic leukemia

Neutrophil myeloperoxidase from a patient with chronic myelocytic leukemia was isolated under conditions designed to minimize proteolysis. Those methods yielded an α₂β₂ form of myeloperoxidase from normal individuals. Purified enzyme from the patient had electronic absorbances ($\text{A}{}_{430}\text{A}{}_{280}\text{= 0.85}$), enzymatic activity, and electrophoretic and Chromatographic behavior indistinguishable from that of normal myeloperoxidase. Edman degradation and physical studies after reduction and denaturation, however, showed that as compared to normal enzyme, one 55,000-dalton α subunit of the patient's myeloperoxidase was replaced by a 39,000-dalton peptide with a different amino-terminal sequence, a mixture of smaller peptides, and an heme derivative. Myeloperoxidase from the leukemic neutrophils appeared to have been partially degraded in vivo by lysosomal proteases.