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Clonality and X-inactivation patterns in hematopoietic cell populations
detected by the highly informative M27 beta DNA probe [see comments]
MF Fey, S Liechti-Gallati, A von Rohr, B Borisch, L Theilkas, V Schneider, M Oestreicher, S Nagel, A Ziemiecki and A Tobler
Institute of Medical Oncology, Inselspita, Berne, Switzerland.
About 80% to 90% of females are informative for X- inactivation/methylation
analysis with the probe M27 beta, which would therefore seem attractive in
assessing clonality in hematologic cell populations. Eighteen acute
lymphoid or myeloid leukemias, three chronic lymphocytic leukemias, and
three chronic myelogenous leukemias as well as 12 malignant non-Hodgkin's
lymphomas mostly showed extremely skewed clonal X inactivation (median
allelic cleavage ratio [ACR] of unmethylated/inactive M27 beta alleles was
50, range 1 to 100) or hypermethylation of both alleles. Two lymphomas
showed random M27 beta X inactivation but clonal antigen-receptor gene
rearrangements. In normal peripheral blood leukocytes from 105 healthy
females aged 2 to 96 years, the median ACR was 2 (range 1 to 100). Thus, it
was significantly lower than in the leukemias (P = .0001, Mann-Whitney
test), but extremely skewed patterns (ACR > 10.8, ie, > 80th
percentile) were seen not only in the leukemias but also in 21/105 samples
(20%) of normal leukocytes, and significantly more frequent in a population
of elderly women (aged 75 to 96 years) compared with healthy children (aged
2 to 8 years) and younger women (aged 20 to 58 years) (P = .00125; chi 2
test). We conclude that in a population of cells derived from the
hematopoietic system where clonality is uncertain, skewed M27 beta patterns
are not reliable indicators for the presence of a clonal neoplastic
disorder. The basis for severe X- inactivation skewing is unclear at
present, but this finding raises interesting questions regarding the
composition of the hematopoietic stem cell pool.
Volume 83,
Issue 4,
pp. 931-938,
02/15/1994
Copyright © 1994 by The American Society of Hematology
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