Variability of the molecular defects corresponding to the presence of a
Philadelphia chromosome in human hematologic malignancies
G Saglio, A Guerrasio, A Tassinari, C Ponzetto, A Zaccaria, P Testoni, B Celso, G Rege Cambrin, A Serra and L Pegoraro
Dipartimento di Scienze Biomediche e Oncologia Umana, Universita di Torino,
Italy.
By analyzing a total of 107 patients affected by chronic myelogenous
leukemia (CML; chronic and blast crisis) or lymphoid and myeloid
Philadelphia chromosome (Ph') positive acute leukemias, we have
investigated the relationship between the molecular defect on the Ph'
chromosome and the associated hematologic phenotype. As expected,
approximately half of the Ph' positive acute leukemias showed a breakpoint
on chromosome 22 falling outside the "breakpoint cluster region" (bcr)
known to be involved in CML. Surprisingly, seven of 80 CML cases in chronic
phase also showed rearrangements falling outside the bcr region. In two of
these cases the breakpoint on chromosome 22 was mapped between 9 and 12 kb
upstream to the bcr region. In another case, the breakpoint was located
approximately 16 kb downstream to bcr. In the remaining four cases, the
precise position of the rearrangement could not be localized with the
available bcr probes. DNAs from patients with CML blast crises showed
classical bcr rearrangements. No molecular changes were observed during the
progression of the disease in six patients whose DNA from both a chronic
and acute phase was available. Our results seem to indicate a greater
degree of variability of chromosome 22 breakpoints in CML than previously
observed, and the lack of additional rearrangements on the Ph' chromosome
in CML blast crises with respect to chronic phase.
Volume 72,
Issue 4,
pp. 1203-1208,
10/01/1988
Copyright © 1988 by The American Society of Hematology
