Variable Philadelphia breakpoints and potential lineage restriction of bcr
rearrangement in acute lymphoblastic leukemia
LM Secker-Walker, HM Cooke, PJ Browett, CA Shippey, JD Norton, E Coustan-Smith and AV Hoffbrand
Department of Haematology, Royal Free Hospital School of Medicine, London,
UK.
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.
Volume 72,
Issue 2,
pp. 784-791,
08/01/1988
Copyright © 1988 by The American Society of Hematology
