High expression of transforming growth factor-beta long cell cycle times
and a unique clustering of S-phase cells in patients with acute
promyelocytic leukemia [see comments]
A Raza, N Yousuf, A Abbas, A Umerani, A Mehdi, SA Bokhari, Y Sheikh, K Qadir, J Freeman and M Masterson
University of Cincinnati, OH.
Expression of transforming growth factor-beta (TGF-beta), which inhibits
the proliferation of hematopoietic progenitors, was investigated
simultaneously with cell cycle characteristics in 63 bone marrow biopsies
from 23 cases with acute promyelocytic leukemia (APL). Bromodeoxyuridine
(BrdU) was administered to every patient (17 newly diagnosed) for
determination of the labeling index (LI) and the durations of S-phase (Ts)
and the cell cycle (Tc) of leukemic promyelocytes. APL cases had lower LI
both in the bone marrow aspirate (6.1% v 11.4%, P = .008) and biopsy (21.1%
v 28.0%, P = .001) and longer Tc (93.6 hours v 56.0 hours, P = .002) when
compared with other French-American-British subtypes. TGF-beta expression
(detected by a monoclonal anti-TGF-beta 2/beta 3 antibody) was dramatically
high, especially in interstitial areas of the biopsies. S-phase cells were
found as geographically restricted islands of proliferation (GRIPs) in 20
of 22 cases. Weekly biopsies showed an increment in TGF-beta on day 7 of
therapy in 13 of 17 cases, while in vivo differentiation was noted in 9 of
15. We conclude that the presence of high TGF-beta expression may explain
the biologic basis for the slowly cycling nature of leukemic promyelocytes
in APL as well as the unique clustering of S- phase cells observed in
GRIPs.
Volume 79,
Issue 4,
pp. 1037-1048,
02/15/1992
Copyright © 1992 by The American Society of Hematology
