Chromosome studies in Alzheimer's disease patients: distribution of dicentric breakpoints in lymphocytes irradiated in vitro.

A previous study showed a significant increase in dicentric frequency in lymphocytes irradiated in vitro from non-familial Alzheimer's disease patients compared to normal age-matched controls. This study examined the distribution of the chromosome breakpoints involved in the dicentric formation and found a non-specific increase in all chromosomes.

Demonstration of acquired hemizygosity and clonality in acute lymphoblastic leukemia with chromosome 7 abnormalities using hypervariable DNA probes.

Clonal abnormalities of chromosome(s) 7 were investigated in two patients with acute lymphoblastic leukemia. The abnormal karyotypes were 46,XY,-7,del(6)(q13q21), + i(7q)/47,XY,del(6), + i(7q) in case 1, and 46,XX,-7,t(4;11)(q21;q23), + i(7q) in case 2. DNA from leukemic tissue was investigated with Southern blotting using hypervariable DNA probes lambda MS31 and p lambda g3 located on 7p and 7q, respectively. Restriction fragment length polymorphisms (RFLPs) were detected on the short arm in case 1 and on both arms in case 2, and a marked difference in intensity between the two alleles was observed. In case 1 the acquired hemizygosity of 7p, suggested by the cytogenetic findings, was confirmed by Southern blotting. Thus, one chromosome 7 formed the i(7q) and the other No. 7 was duplicated. In case 2 the results of the Southern blotting indicated that the size of the clone with i(7q) was considerably greater than suggested by cytogenetic analysis of the few available metaphase cells.

Leukemia characterized by multiple sub-clones with unbalanced translocations involving different telomeric segments: case report and review of the literature.

A 68-year-old man presented with t(4;11)(q21;q23), B-lineage acute lymphoblastic leukemia (ALL) which was negative for C-ALL antigen and TdT. Clonal evolution to five different, but related karyotypes, in which chromosomal material distal either to 1q11 or 1q21 was translocated to the terminal regions of 4q-, 11q, 16q, and 19p resulted in partial or total trisomy of 1q. The patient, having achieved a short remission, died 14 weeks after diagnosis. Five reports of jumping translocations in hematological malignancies, four with B-lineage malignancy, are reviewed. One (four cases) or both (one case) of the same 1q breakpoints were consistently found and 11q and 16q were repeatedly involved. Such cases, having multiple subclones with trisomy 1q, may form a distinct subgroup of ALL.

Isochromosome 9q in acute lymphoblastic leukemia: a new non-random finding.

The presence of an isochromosome is commonly associated with late-stage disease and has rarely been reported at diagnosis in hematological malignancies. Five patients (two males and three females aged 3, 6, 13, 13, and 35 years) with an acquired i(9q) at diagnosis of acute lymphoblastic leukemia (ALL) are presented; in one case it was the sole karyotypic change. The patients presented in November or January, two in 1983/84, three in 1987/88. The latter were three of 100 unselected ALL cases referred over a three year period for cytogenetics and successfully karyotyped. Two had a prior history of pancytopenia. Features of high risk ALL in these patients included age over 10 years (three cases), leukocyte counts greater than 200 x 10(9)/liter (two cases) and pre-B immunological phenotype (two cases). All achieved remission on standard protocols. One patient is disease free over 4.5 years from diagnosis. One relapsed at 3.5 years and is well following a bone marrow transplant in second remission. Follow-up for the remaining three patients is between 9 and 11 months. Our findings indicate that i(9q) frequently with additional chromosome change is a feature of newly diagnosed ALL.

Variable Philadelphia breakpoints and potential lineage restriction of bcr rearrangement in acute lymphoblastic leukemia.

Philadelphia (Ph1) chromosome breakpoints in acute lymphoblastic leukemia (ALL) are of two kinds: those within the breakpoint cluster region (bcr+), as in chronic myeloid leukemia (CML), and those outside it (bcr-). These encode different c-abl messenger RNAs (mRNAs), p210 and p190, respectively. It has been suggested that one class of Ph+ ALL (bcr+) may be a variant of CML arising in a multipotent stem cell, the other (bcr-) de novo ALL initiated in a lymphoid-committed progenitor. Thirty-two cases of ALL (12 Ph1+, ten chromosomally normal, and ten non-mitotic cases) were investigated for bcr involvement. Breakpoints were found within five Ph1+ and in one normal case. There was no difference in clinical features, common ALL antigen (CALLA) positivity, cytogenetics, or response to treatment between the 6 bcr+ and 7 Ph1+ bcr- patients. Myeloid antigen expression was found in 2 bcr+ cases. Bcr rearrangement appeared to be restricted to the lymphoblastic component of marrow or blood in at least four bcr+ cases. In one case, separated myeloid and lymphoid cell fractions were both bcr+. Potential heterogeneity of the Ph1+ target cell, as seen in this study, may be more important in determining disease outcome than the precise location of the Ph breakpoint.