ASSOCIATION OF PML-RAR-ALPHA FUSION MESSENGER-RNA TYPE WITH PRETREATMENT HEMATOLOGIC CHARACTERISTICS BUT NOT TREATMENT OUTCOME IN ACUTE PROMYELOCYTIC LEUKEMIA - AN INTERGROUP MOLECULAR STUDY
Re. Gallagher et al., ASSOCIATION OF PML-RAR-ALPHA FUSION MESSENGER-RNA TYPE WITH PRETREATMENT HEMATOLOGIC CHARACTERISTICS BUT NOT TREATMENT OUTCOME IN ACUTE PROMYELOCYTIC LEUKEMIA - AN INTERGROUP MOLECULAR STUDY, Blood, 90(4), 1997, pp. 1656-1663
In each case of acute promyelocytic leukemia (APL) one of three PML-RA
R alpha mRNA types is produced, depending on the break/fusion site in
the PML gene that is linked to a common RAR alpha gene segment: a shor
t (S)-form type, PML exon 3 RAR alpha exon 3; a long (L)-form type, PM
L exon 6 RAR alpha exon 3; or a variable (V)-form type, variably delet
ed PML exon 6 RAR alpha exon 3. We evaluated whether PML-RAR alpha mRN
A type is associated with distinct pretreatment clinical characteristi
cs and therapeutic outcome in previously untreated adult APL patients
registered to protocol INT 0129 by the Eastern Cooperative Oncology Gr
oup, the Southwest Oncology Group, and the Cancer and Leukemia Group S
, Of 279 clinically eligible cases, 230 were molecularly evaluable, an
d of these, 111 were randomized to receive remission induction therapy
with all-trans retinoic acid (ATRA) and 119 with conventional chemoth
erapy. Nine cases Plot excluded by central pathology review were PML-R
AR alpha negative, and notably, none of five of these cases treated wi
th ATRA achieved complete remission (CR). Among 221 PML-RAR alpha-posi
tive cases, there were 82 S-farm cases (37%), 121 L-form cases (55%),
and 18 V-form Gases (8%). Before any antileukemic therapy, the S-form
type, compared with the L-form type, was associated with higher Values
for the white blood cell (WBC) count (median 2,500/mu L v 1,600/mu L;
P = .009), the percentage of blood blasts plus promyelocytes (median
29% v 8.5%; P = .03), and the absolute blood blasts plus promyelocytes
(884/mu L v 126/mu L;, P = .019). also, an increased percentage of S-
form versus L-form cases had the M3 variant phenotype, 24% v 12% (P =
.036). There were net differences between S-form and L-form cases in e
ither CR rate (79% v 69%; P = .14) or disease free survival distributi
on (multivariate analysis adjusting for the association of S-form type
and higher WBC count; P = .40). We conclude that the S-form type is a
ssociated with previously-identified adverse risk WBC parameters but t
hat the identification of the S-form or L-form type of PML-RAR alpha m
RNA, per se, does not predict clinical outcome or add to the value of
an increased WBC count as a negative prognostic indicator in APL patie
nts. (C) 1997 by The American Society of Hematology.