The pathogenesis of acute leukemia is still poorly understood. In the
past few years several groups have reported deletion of the RB1 gene o
r altered pRB expression in certain hematologic malignancies, suggesti
ng a possible role of RB1 gene inactivation in the process of leukemog
enesis. Most studies regarding structural abnormalities of the RB1 gen
e indicate that gross deletions or rearrangements are present in a sma
ll percentage of patients with acute myeloid leukemia (AML), as is the
case with retinoblastoma, where the majority of RB1 gene abnormalitie
s are attributed to point mutations. To investigate if such point muta
tions in the RB1 gene may have a role in leukemogenesis in AML, we scr
eened the RB1 gene of 36 AML patients using conformation-sensitive gel
electrophoresis (CSGE). No point mutations were found in the 27 exons
, their flanking intron regions or in the promoter region in any of th
e 36 patients. Thus, according to our findings, the susceptibility in
these patients for developing AML does not appear to be related to poi
nt mutations in the RB1 gene. While screening for point mutations, we
identified a number of new and previously noted neutral sequence varia
tions indicating the efficiency and sensitivity of CSGE in identifying
small changes in the RB1 gene. (C) 1998 Elsevier Science Ltd. All rig
hts reserved.