R. Bernstein

Abnormalities of chromosome 12p 13 and malignant proliferation of eosinophils: a nonrandom association

Summary. Four patients representing a spectrum of haematological malignancies are reported. Two patients had Philadelphia chromosome negative myeloproliferative disorders, one had acute lymphoblastic leukaemia and one had eosinophilic leukaemia. In each case eosinophilia was present and demonstrated to be part of the malignancy by the association of clonally abnormal metaphases with eosinophil granules. Abnormalities involving the short arm of chromosome 12 (12p 13) were a constant feature in all four cases and therefore a nonrandom association between this chromosome region and malignant eosinophil proliferation is proposed.

Female phenotype and multiple abnormalities in sibs with a Y chromosome and partial X chromosome duplication: H--Y antigen and Xg blood group findings.

A mentally retarded female child with multiple congenital abnormalities had an abnormal X chromosome and a Y chromosome; the karyotype was interpreted as 46,dup(X)(p21 leads to pter)Y. Prenatal chromosome studies in a later pregnancy indicated the same chromosomal abnormality in the fetus. The fetus and proband had normal female genitalia and ovarian tissue. H--Y antigen was virtually absent in both sibs, a finding consistent with the view that testis-determining genes of the Y chromosome may be suppressed by regulatory elements of the X. The abnormal X chromosome was present in the mother, the maternal grandmother, and a female sib: all were phenotypically normal and showed the karyotype 46,Xdup(X)(p21 leads to pter) with non-random inactivation of the abnormal X. Anomalous segregation of the Xga allele suggests that the Xg locus was involved in the inactivation process or that crossing-over at meiosis occurred.

A unique 8;16 translocation in two infants with poorly differentiated monoblastic leukemia.

Acute monoblastic leukemia is nonrandomly associated with abnormalities involving 11q. Two infants, one a neonate and the other 19 months of age, had the same hitherto undescribed karyotypic abnormality, t(8;16)(p11;p13), associated with acute nonlymphocytic leukemia M5a. The older child had an additional translocation, t(10;11)(q11;p15), but the chromosome arms affected were the opposite to those described in acute nonlymphocytic leukemia M5a of childhood. Therefore, it is postulated that genes involved in monocytic differentiation may be situated on 8p11 or 16p13, as well as on 11q.

Cytogenetic findings in chronic myeloid leukemia (CML); evaluation of karyotype, blast morphology, and survival in the acute phase

Abstract Cytogenetic data on a series of 68 patients with chronic myeloid leukemia (CML) are presented, with emphasis on chromosomal findings in 19 patients who either transformed from a chronic to an acute phase (12 cases) or presented in an acute phase (7 cases). Correlation of chromosome patterns, blast morphology, and survival was attempted, following the aims and recommendations of the First International Workshop in Leukemia (Cytogenet Cell Genet (1977): 19, 321). A Philadelphia (Ph 1 ) chromosome was detected in 61 of 68 patients (90%) and identified by banding in 40 cases; 39 patients had the usual (9;22) translocation and one patient showed an unusual (17;22) Ph 1 translocation. Clonal abnormalities in addition to the Ph 1 were found in 9% of chronic patients whereas 79% of acute patients showed karyotypic clonal evolution. The three most frequently observed patterns of clonal evolution were trisomy 8, two Ph 1 chromosomes and an isochromosome 17 (i(17q)). Two Ph 1 chromosomes were observed in both chronic and acute cases, but in this series, trisomy 8 and i(17q) were detected only in acute patients. Detection of clonal evolution is generally indicative of an accelerated phase in the majority of cases and the development of an i(17q) clone is particularly ominous. After transformation, no obvious correlation between the pattern of clonal evolution, blast morphology, or survival was found.

Karyotype analysis in acute nonlymphocytic leukemia (ANLL): Comparison with ethnic group, age, morphology, and survival

The karyotype, leukemia cell morphology (FAB classification), ethnic group, age, sex, and survival were compared in 60 patients with acute nonlymphocytic leukemia (ANLL), to determine their diagnostic and prognostic significance. An ethnic age difference was observed; a significantly greater number of black patients were children. The majority of children were males. A higher frequency of chromosome abnormalities was detected in children, yet they survived longer than adults. A specific, significant association between a (8; 21) karyotype and M2-ANLL was confirmed; four of ten patients with M2-ANLL showed this translocation. The more mature morphology of M2-ANLL was associated with a longer survival irrespective of karyotype, ethnic group, and age. The specificity of t(15; 17) in M3-ANLL and nonrandom monosomy 7 in preleukemic children was confirmed. Patients, particularly adults, with normal karyotypes tended to survive longer than those with abnormal karyotypes. The patients age and the differentiative capacity of the leukemic cell appear to be as important as the karyotype in determining survival. The nonrandom association of certain chromosome aberrations in ANLL appears to be worldwide.

Acute megakaryoblastic leukaemia with 3q inversion and elevated thrombopoietin (TSF): an autocrine role for TSF?

Summary. A patient with acute megakaryoblastic leukaemia is described in whom exactly the same paracentric inversion of 3q was detected as in three previously documented cases. The patients serum thrombopoietin (TSF) was significantly raised. Based on these findings we postulate a role for a gene (? oncogene) on chromosome 3q in thrombopoietin production. Abnormalities of 3q may assist in delineating a subgroup of acute nonlymphocytic leukaemia, namely acute megakaryoblastic leukaemia.

Abnormalities of Chromosome 7 Resulting in Monosomy 7 or in Deletion of the Long Arm (7q-): Review of Translocations, Breakpoints, and Associated Abnormalities

In summary, of 64 patients with total or partial monosomy 7, 21 cases showed a deletion of 7q, and a translocation resulting in loss of the whole or major portion of 7q was detected in six other cases; a consistent translocation involving chromosomes #7 and #17 was observed in four of the latter cases, resulting in an effective loss of 7q. In 23 of these 27 patients reviewed with loss of 7q, the common segment deleted involved 7q32 to 7q34 (Table). The most common abnormalities associated with -7 or 7q- were -5 or 5q- (26 cases) and monosomy 17 (16 cases); except for two patients, all of the latter also had -5 or 5q-. Fifteen of the 64 patients with -7 or 7q- had a secondary leukemia (23.4%). Other abnormalities, such as complete and partial trisomy 7 and various balanced translocations involving #7, were far less common. Only one of 16 cases had an associated 5q- chromosome, one was -17, and only one case had secondary leukemia.

Inverted Y chromosome polymorphism in the Gujerati Muslim Indian population of South Africa.

SummaryAn inverted Y chromosome has been found at a very high frequency in a Muslim Indian community living in the Johannesburg-Witwatersrand area of the Transvaal Province of South Africa: 8 of 141 (5.7%) retrospectively identified Indian males had an inv(Y)(p11.2q11.23) and all were of the Muslim faith. The inversion was found in 22 of 72 (30.5%) prospectively studied normal Muslim Indian males. All the carriers of the inversion were Gujarati-speakers whose families migrated to the Transvaal from the Gujerat Province of India during the first half of this century. The origins of the ancestors of the individuals with inv(Y) were traced to a small village, Kholvad, near the city of Surat, and some neighbouring villages. The polymorphic frequency of the inv(Y) has probably been produced through random genetic drift in a reproductively isolated community, maintained by strict endogamous marriage customs based on religious and linguistic affiliations. There was no indication that the inverted Y was associated with any reproductive disadvantages.

Fanconi's anemia—Chromosome breakage studies in homozygotes and heterozygotes

The in vitro enhancement of chromosome breakage by diepoxybutane (DEB) and mitomycin C (MMC) was studied in 24 Fanconis anemia (FA) homozygotes and 28 heterozygotes. Both drugs were shown to enhance chromosome breakage significantly in the homozygotes. In the great majority of cases, DEB and MMC stressing are reliable techniques for the definitive cytogenetic diagnosis of FA homozygosity. However, the present study provides no evidence that individual FA heterozygotes can be differentiated from normal individuals on the basis of spontaneous, DEB- or MMC-induced chromosome breakage.

The PLC/PRF/5 human hepatoma cell line. II. Chromosomal assignment of hepatitis B virus integration sites

The chromosomal sites at which hepatitis B virus (HBV) DNA is integrated into the genome of the hepatocellular carcinoma (HCC) cell line, PLC/PRF/5 were investigated in an attempt to understand the mechanisms by which hepatitis B virus may induce malignant transformation. In situ hybridization of an HBV DNA probe to metaphase chromosomes of the PLC/PRF/5 cell line, followed by statistical analysis, identified three integration sites; these were 15q22-q23, 11q22, and 18q12. In particular, hybridization to chromosome #15, which is present in four copies in complete metaphases of this cell line, was highly significant (p much less than 0.0005).