Hiroshi Takatsuki

Deletion of chromosome 6q in two cases of acute myeloblastic leukemia and a review of the literature.

Two cases of acute myeloblastic leukemia (AML M2) associated with a deletion of chromosome 6q are described. One was a 38-year-old man with constitutional inversion of chromosome 9, and another was a 57-year-old female atomic-bomb survivor. The karyotype of these patients were 46,XY,del(6)(q12q14),inv(9)(p11q13), and 47,XX,6q-,+min, respectively. In both cases c-myb protooncogene, which is located in chromosome 6q, was neither deleted nor rearranged, and c-myb messenger RNA level was not elevated. These results suggest that c-myb is not involved in the leukemogenesis of AML with 6q- as well as lymphoid malignancies with 6q-. Out of 23 AML cases with 6q- reviewed, 6 cases had erythroleukemia, and 4 developed in Down syndrome patients.

A case of insulin allergy: the crystalline human insulin may mask its antigenicity

We report an unusual case of insulin allergy. A 48-year-old man with non-insulin-dependent diabetes mellitus receiving biosynthetic isophane human insulin (Humulin N) developed itchy wheal-and-flare reactions at the sites of injection. When Humulin N was changed to a semi-synthetic crystalline human insulin zinc (Novolin U), the allergic reactions completely disappeared. Evaluation of his serum showed a high level of insulin-specific IgE. Skin testing with all commercially available insulins showed immediate local reactions to all agents tested except for Novolin U. In addition, decrystallized Novolin U prepared by lowering the pH with acetic acid also induced a positive reaction. These observations suggest that the crystallized structure of human insulin may mask its antigenicity for allergic reactions.

Monitoring minimal residual disease in patients with MLL-AF6 fusion transcript-positive acute myeloid leukemia following allogeneic bone marrow transplantation.

Acute myeloid leukemia (AML) patients with chromosome 11q23 abnormalities or MLL rearrangements have a poor prognosis when treated with conventional chemotherapy. However, the efficacy of allogeneic bone marrow transplantation (BMT) for this type of leukemia is not yet clear.We describe 2MLL-AF6 fusion transcript-positive AML patients treated with allogeneic BMT who were monitored for minimal residual disease (MRD) by reverse transcriptase polymerase chain reaction. Although long survival or cure of this type of AML is rarely reported, 1 patient had durable remissions. Fusion transcripts disappeared in 1 patient but not in the other, even after the graft-versus-host disease effect was increased by the discontinuation of immmunosuppressive therapy. This is the first report of MRD and the probability of graft-versus-leukemia effects following BMT in AML patients who areMLL-AF6 fusion transcript positive.

Which progenitor is the target cell in the development of acute promyelocytic leukemia

Acute promyelocytic leukemia (APL) is characterized by the t(15;17) which involves the PML gene and the retinoic acid receptor alpha (RAR alpha) gene, and the subsequent PML/RAR alpha fusion gene is a key event in the leukemogenesis of APL. We found that the PML/RAR alpha fusion gene was expressed in both granulocytic/macrophage and erythroid colonies in a few patients with APL. In some instances of acute myelogenous leukemia (AML), erythrocytes or platelets also expressed the glucose-6-phosphate dehydrogenase (G-6-PD) isoenzymes which were detected in the leukemic cells. Some APL cells show basophilic and monocytoid differentiation and these findings suggest that the leukemic precursor of APL is derived from a more primitive cell stage than the promyelocyte. The precursor cells appear to be derived from heterogeneous levels.

Recurrent appearance of 14q+ chromosome associated with lymphoid crisis of Ph-positive chronic myelogenous leukemia.

The 14q+ chromosomal anomaly commonly found in cases of lymphoid neoplasm recurrently occurred during the lymphoid crisis of a patient with Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML). At presentation lymphoblasts, with pre-B phenotype increased, and both the Ph and 14q+ were found in the same metaphases. After treatment with vincristine and prednisolone, the patient entered into the chronic phase, and only a Ph was detected in 100% of the cells examined. The 14q+ reappeared at the recurrence of the lymphoid crisis, and then disappeared in the second chronic phase. The BCR/ABL mRNA, which is specific for CML, was detected in the blastic cells by a method using reverse transcriptase and polymerase chain reaction. The rearrangement of the immunoglobulin heavy chain gene (JH gene) was also detected in the blastic cells. These results suggest that the 14q+ was closely associated with the lymphoid crisis of the CML patient.