mercaptopurine and Leukemia--Megakaryoblastic--Acute

Overexpression of v-ski blocks the terminal differentiation of chicken erythroblasts, and in cooperation with v-sea causes transformation of these cells, indicating that c-ski may play a role in regulating either proliferation or differentiation in hematopoietic cells. We examined c-ski expression in four different myeloid cell lines which can be induced to differentiate by exposure to phorbol 12-myristate 13-acetate (PMA). Two of the cell lines are multipotent and have the ability to differentiate into either erythrocytes or megakaryocytes (K562 and HEL cells), one cell line differentiates exclusively into megakaryocytes (CHRF-288-11), and the fourth cell line differentiates into either monocytes or granulocytes (HL-60). Our findings indicate that c-ski mRNA is up regulated by PMA only in those cell lines which respond by differentiating along the megakaryocyte lineage. The extent of differentiation and the observed increase in c-ski mRNA levels are positively correlated with the PMA concentration used to induce differentiation. Experiments in which CHRF-288-11 cells were treated with the protein kinase C (PKC) activator bryostatin 1 indicate that c-ski mRNA induction is not a general effect of PKC activation. The results strongly suggest that c-ski expression is correlated with megakaryocyte maturation.

Topics: Bryostatins; Cell Differentiation; Culture Media; Dose-Response Relationship, Drug; Humans; Lactones; Leukemia, Megakaryoblastic, Acute; Macrolides; Megakaryocytes; Membrane Glycoproteins; Mercaptopurine; Proto-Oncogene Mas; Proto-Oncogenes; RNA, Messenger; Tetradecanoylphorbol Acetate; Time Factors; Tumor Cells, Cultured

In a 4-year-old girl having acute megakaryoblastic leukemia, recombinant human granulocyte colony-stimulating factor (G-CSF) was used in combination with chemotherapy for remission induction after the second relapse of her leukemia. G-CSF was given intravenously at a dose of 100 micrograms/m2/day 24 hours prior to chemotherapy until the peripheral neutrophil counts fully recovered. Cytosine arabinoside (Ara-c) [100mg/m2/day] and VP-16 [100mg/m2/day] were given from day 1 through day 10. Her leukemia was resistant to chemotherapy alone after the second relapse but complete remission and hematological recovery were achieved two months after the start of this therapy. Although in vitro clonal assay did not show significant stimulation of colony formation by G-CSF on leukemia cells of this patient, and the mechanism underlying remission induction by this combination therapy remains unclear, it may be of benefit to use G-CSF in combination with chemotherapy for patients with drug-resistant leukemia.

Topics: Antineoplastic Combined Chemotherapy Protocols; Child, Preschool; Cytarabine; Doxorubicin; Drug Resistance; Female; Granulocyte Colony-Stimulating Factor; Humans; Leukemia, Megakaryoblastic, Acute; Mercaptopurine; Prednisolone; Remission Induction

A case of congenital leukemia with monosomy 7 is reported. Immunological study of the blast cells using monoclonal antibodies was suggestive of both myelomegakaryocytic and T-lymphoblastic leukemia. Chromosomal analysis of the bone marrow cells showed monosomy 7. Chemotherapy was initiated with a combination of adriamycin, cytosine arabinoside, 6-mercaptopurine, and prednisolone. The patient obtained complete remission, which has been maintained for 4 years and 1 month. He receives no chemotherapy now. Our case shows that monosomy 7 in congenital leukemia is rare, but the presence of monosomy 7 in congenital leukemia does not necessarily indicate a poor prognosis.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chromosomes, Human, Pair 7; Cytarabine; Doxorubicin; Humans; Infant, Newborn; Karyotyping; Leukemia; Leukemia-Lymphoma, Adult T-Cell; Leukemia, Megakaryoblastic, Acute; Male; Mercaptopurine; Monosomy; Prednisolone; Remission Induction

Three cases of secondary leukemia developing after chemotherapy and/or radiotherapy for myeloma, mycosis fungoides, and non-Hodgkin's lymphoma are reported. The first case was a 51-year-old man with IgG-lambda myeloma, treated with melphalan and prednisolone, who developed acute myelomonocytic leukemia 54 months after the diagnosis of myeloma. The second case was a 54-year-old woman with mycosis fungoides treated with radiation, predonine, and cyclophosphamide, who developed acute megakaryoblastic leukemia 298 months after the diagnosis of mycosis fungoides. The third case was a 35-year-old woman with stage IV non-Hodgkin's lymphoma treated with VEMP who developed acute myelogenous leukemia 26 months after the diagnosis of malignant lymphoma. All cases showed pancytopenia and two of three cases had morphologic abnormality in several hemopoietic cell lineages in the leukemic stage. There is a possibility that second malignancies are an increasingly recognized complication in the patients treated with a large amount of chemo-radiotherapy.

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Female; Humans; Leukemia; Leukemia, Megakaryoblastic, Acute; Leukemia, Myeloid, Acute; Leukemia, Radiation-Induced; Lymphoma, Non-Hodgkin; Male; Melphalan; Mercaptopurine; Middle Aged; Multiple Myeloma; Mycosis Fungoides; Pancytopenia; Prednisolone; Vincristine