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.

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.

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.

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