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The presence of an altered Hox-2.4 gene in the WEHI3B murine myeloid leukemia suggests that homeobox genes may contribute to neoplasia. A survey of 31 leukemia cell lines of the myeloid, lymphoid and erythroid lineages revealed that Hox-2.4 was expressed only in WEHI3B and the pre-B lymphoid line 70Z/3, in which no DNA rearrangement was observed. To clarify the WEHI3B alteration and normal Hox-2.4 structure, we have sequenced near full length cDNA clones from WEHI3B and 70Z/3, and the 5' portion of the normal Hox-2.4 gene. A WEHI3B cDNA clone demonstrates that an intracisternal A-particle (IAP) provirus has inserted within the first exon of the gene and generated a Hox-2.4 mRNA with a 5' sequence derived from the IAP long terminal repeat. A remarkable degree of similarity found between the amino acid sequences of Hox-2.4 and Hox-3.1, which reside on different chromosomes, supports the notion that an ancient homeobox gene cluster has been duplicated and dispersed early in vertebrate evolution.

A monoclonal antibody-secreting hybrid cell line, E7, was constructed from myeloma cells and spleen cells from BALB/c mice immunized with partially purified human MIF from culture fluid of the human T-lymphoblast cell line Mo. The hybrid cell line E7 was selected by screening hybridoma cultures for their capacity to adsorb added MIF activity when assayed together with rabbit anti-mouse IgG-coupled to protein A-Sepharose. The monoclonal antibody produced by the cloned hybridoma E7 also directly neutralized MIF activity from Mo cells and two species of MIF from the culture fluid of human peripheral blood lymphocytes, but did not neutralize IFN-gamma from Mo cells and from human peripheral blood lymphocytes. This antibody reacted also with a component in phytohemagglutinin preparations with an apparent molecular weight of 60,000; however, it did not react with the active tetramer of phytohemagglutinin.

This report demonstrates a case of transient abnormal myelopoiesis (TAM) evolving in a patient with Down's syndrome. A diagnosis was established after the patient's blast cell count decreased considerably three weeks after the initial leukemic phase. The blast population in the authors' case expressed Leu-9 (CD7), 6D1, and TdT+. Cytochemistries showed some of the blast population to be peroxidase positive and Sudan black positive. Platelet peroxidase by electron microscopic examination showed some positive blasts. Therefore, surface markers and cytochemical studies in this case suggested an abnormal proliferation involving a pluripotential stem cell capable of expressing myeloid and lymphoid characteristics. Cytogenetics was performed at birth and showed 47,XY,+21/48,XY,+21,+mar, confirming the diagnosis of Down's syndrome. The origin of the chromosomal fragment was uncertain. It was of interest that during the remission phase of his pseudoleukemia there was a concomitant decrease in the extra chromosomal fragment. Immunoglobulin and T-cell antigen receptor gene rearrangement studies showed only germline patterns, indicating that the lymphoid cells in the blast population were not clonally expanded. Therefore, immunoglobulin and T-cell antigen receptor rearrangement analysis and immunophenotyping are extremely valuable techniques in distinguishing between TAM and acute lymphoblastic leukemia in patients with Down's syndrome.

The expression of myeloid differentiation antigens on acute nonlymphocytic leukemia cells (ANLL) was analyzed with four distinctive monoclonal antibodies (MoAbs); YM-1, HL-1, 20.2 and 20.3. These four MoAbs were shown to recognize different stages of differentiation of myeloid progenitor cells (CFU-GM) and/or mature myeloid cells. Consequently, leukemia cells of 68 adult patients with ANLL were able to be divided into four groups according to their expression of the antigens defined by these MoAbs: group 1 HL-1(-), YM-1(-), 20.2(-), 20.3(-) (13 cases); group 2 HL-1(+), YM-1(-), 20.2(-), 20.3(-) (16 cases); group 3 HL-1(+), YM-1(+), 20.2(-), 20.3(-) (13 cases) and group 4 HL-1(+), YM-1/20.2/20.3(+/(-)) (26 cases). This classification elucidated not only the maturation stages of ANLL but also the diversity of ANLL. When compared with the morphological classification, acute myeloblastic leukemia (AML) cases (M1 and M2 of the FAB classification) were evenly distributed among all four groups. These data suggest that the AML group was composed of heterogeneous leukemias which expressed surface phenotypes of different maturation stages ranging from the most immature stage to the mature stage. In contrast, the mature type (group 4) was composed of not only AML (M1 and M2), but also acute monocytic leukemia (M4) and acute myelomonocytic leukemia (M5). The clinical courses of these 68 patients revealed that the complete remission rate, remission duration and survival time were not significantly different among the four groups.