To determine whether one or more hematopoietic-cell lineages are involved in acute myeloid leukemia (AML), we designed a technique that simultaneously identifies a cell as malignant and determines its lineage. We used numerical clonal chromosomal abnormalities, which are readily detected, to indicate neoplasia, and monoclonal antibodies in an alkaline phosphatase-antialkaline phosphatase detection procedure to identify lineages as granulocytic-monocytic, erythrocytic, or megakaryocytic. Examination of bone marrow from 12 patients with AML showed metaphases of granulocytic-monocytic lineage with abnormal karyotypes in all patients. In seven patients, we also detected abnormal karyotypes in the erythrocytic or megakaryocytic lineage. In all four patients with monosomy 7, both granulocytic-monocytic and erythrocytic cells were affected. Two of four patients with trisomy 8 also had evidence of multiple-lineage involvement, but in two the erythrocytic lineage had normal karyotypes, suggesting an origin at a progenitor-cell stage committed to granulocytic-monocytic development. Multiple-lineage involvement was found in AML both arising de novo (four of five analyzable cases) and following another cancer (three of four analyzable cases). These data demonstrate multiple-lineage involvement in a high proportion of cases of AML and suggest that many cases originate from the multipotent hematopoietic cell or from an earlier progenitor cell.

The identification of recurring chromosomal translocations has provided clues to the gene regions important in lymphoma development. Among 157 patients with non-Hodgkin lymphoma studied by cytogenetic analysis, four new recurring translocations have been identified--t(8;9) (q24;p13), t(11;18)(q21;q21), t(14,15)(q32;q15), and an unbalanced translocation giving rise to der(22)t(17;22) (q11;p11). Each translocation appeared twice. The t(11;18) was the only karyotypic abnormality in the two patients with it, and the t(14;15) was the sole karyotypic abnormality in one patient. All translocations were found in B-cell malignancies and were associated with both nodal and extranodal disease. Among the regions affected, only the immunoglobulin heavy- chain gene MYC, and BCL2, have thus far been associated with lymphoma. The breakpoint sites identified by these translocations warrant further investigation at the molecular level.

The examination of sequential karyotypes in hematologic disorders has demonstrated that karyotypic changes are often associated with concurrent changes in clinical behavior. Acquired abnormalities that recur among different patients may also suggest genomic areas important to tumor progression. We therefore examined sequential karyotypes in 21 patients with non-Hodgkin lymphoma (NHL). Sixteen of the 21 karyotypes demonstrated changes, including the majority of 6 small lymphocytic, 11 follicular, and 4 intermediate and high-grade diffuse lymphomas. The t(14;18)(q32;q21) occurred in ten initial karyotypes was retained in all cases. The band most frequently affected by newly acquired abnormalities was 14q32 (n = 5); chromosomes 1 and 2 (n = 5, each), and the 17p arm (n = 4) were also commonly affected. The acquired deletion of all or part of 17p appeared to be associated with a poor prognosis. Histologic transformation and karyotypic change did not correlate. This study of sequential karyotypes in NHL 1) confirms the primary importance of the t(14;18), 2) suggests that the 14q32 band is involved frequently in both primary and secondary cytogenetic events, and 3) suggests other genomic regions of potential significance to progression.

Of the four male sterile, ms, loci that have been identified in the vermilion region, 9F4 to 10C2, of Drosophila melanogaster, one specifically affects male fertility, whereas three influence male and female fertility and viability. Mutations a t a testis-specific locus (10A2-5; 1-33.44) blocked postmeiotic spermatid maturation at or before the coiling stage. Improper associations of the axonemal sheath with the axoneme and with the mitochondria1 derivatives were common to spermiogenesis in adult ms(l)u3/Y and ms(1)vGIY males representing the locus. Abnormalities in premeiotic events of spermatogenesis were detected in the testes of ms(l)v7lY (9F4 to 9F8-9; 1-32.821, ms(ljv1iY (1-B4-5 to 10B16; 1-34.61), and ms(l)v22/Y and lfllu73iY males (lOB4-5 to 10B16; 1-35.31). Differences in the characteristics of the premeiotic rns mutations suggested that each influences spermatogenesis in a unique way.Estimates indicate that about 15% of the gene loci of Drosophila melanogaster may mutate to a form that is expressed as a male sterile phenotype (Lindsley and Lifschytz, '72; Watanabe and Lee, '77). Male sterile, ms, mutations appeared to be distributed along the X chromosome in a pattern similar to the distribution of lethal loci (Lifschytz and Yakobovitz, '78) in one study, suggesting that many genes can mutate to alleles having lethal or sterile phenotypes. In contrast, several ms loci that affected fertility without altering viability were identified in the proximal region of the X chromosome (Geer et al., '79; Dybas et al., '81). These observations suggest that some genes are directly associated with spermatogenesis, but mutations of other genes may affect male sterility by indirect routes.To examine this possibility, chromosomal region 9F4 to 1OC2, the vermilion, v, region, has been screened extensively for EMS-inducted ms mutations (Geer et al., '82). Mutations a t a locus in 10A2-5 caused male sterility without influencing viability or female fertility. In contrast, rns mutations a t three other loci reduced viability and female fertility and were allelic with lethal mutations. On the basis of these observations two types of ms loci were proposed for the u region: 1) a type A locus, which is concerned specifically with gamete development, and 2) type B loci, which are pleiotropic in nature, The testes of adult males expressing the m s alleles, ms(l)v3 and ms(l)u6, of the presumptive type A locus and ms (ljv7, ms(lju1, Ifl)v73, and ms(l)v22, type B mutations, were examined by light and electron microscopy. Each rns mutation was found to be associated with unique structural deformities, suggesting that the gene products of the ms loci of the u region act independently during sperm development. MATERIALS AND METHODSThe ms strains employed in this study were isolated and characterized by Geer et al. ('82). The ms(l)u7 mutation is located at locus 1 of the u region in 9F4 to 9F8-9 (1-32.82); ms (l)v3 and ms(l)v6 are situated at locus 7 in 10A2 to 10A5 (1-33.44); ms(1)vl is located a t locus 18 in 10B4-5 to 10B1...

The identification of recurring chromosomal translocations has provided clues to the gene regions important in lymphoma development. Among 157 patients with non-Hodgkin lymphoma studied by cytogenetic analysis, four new recurring translocations have been identified--t(8;9) (q24;p13), t(11;18)(q21;q21), t(14,15)(q32;q15), and an unbalanced translocation giving rise to der(22)t(17;22) (q11;p11). Each translocation appeared twice. The t(11;18) was the only karyotypic abnormality in the two patients with it, and the t(14;15) was the sole karyotypic abnormality in one patient. All translocations were found in B-cell malignancies and were associated with both nodal and extranodal disease. Among the regions affected, only the immunoglobulin heavy- chain gene MYC, and BCL2, have thus far been associated with lymphoma. The breakpoint sites identified by these translocations warrant further investigation at the molecular level.