Lineage switch in acute leukemia
S Stass, J Mirro, S Melvin, CH Pui, SB Murphy and D Williams
Conversions of leukemic cell lineage (lymphoid or myeloid) have been
reported only rarely. Our review of the cytochemical and immunophenotypic
features of 89 cases of childhood leukemia in marrow relapse indicated
lineage switch (lymphoid to myeloid or the reverse) in six patients (6.7%).
Five patients with acute lymphoblastic leukemia (ALL) at diagnosis had
converted to acute nonlymphoblastic leukemia (ANLL), and one had converted
from ANLL to ALL. Each child received lineage-specific multiagent
chemotherapy when initially diagnosed, and all achieved a complete
remission. After conversion, four patients readily achieved second
remissions with treatment for the phenotype evident at lineage switch. Two
patients with ANLL at conversion failed ALL-directed reinduction, while one
of the two responded to high-dose cytarabine but died during bone marrow
hypoplasia, emphasizing the importance of prompt recognition of lineage
switch and selection of an appropriate plan of retreatment. Cytogenetic
studies disclosed evidence of clonal selection in one patient and clonal
stability in two. These findings indicate an unexpectedly high frequency of
lineage switch in patients who relapse in the bone marrow after intensive
chemotherapy. Although specific causative factors could not be identified,
our observations suggest at least two general mechanisms for lineage switch
in acute leukemia. In one, chemotherapy appears to eradicate the dominant
clone present at diagnosis, permitting expansion of a secondary clone with
a different phenotype. In the second, drug-induced changes in the original
clone may either amplify or suppress differentiation programs so that
phenotypic shift is possible.
Volume 64,
Issue 3,
pp. 701-706,
09/01/1984
Copyright © 1984 by The American Society of Hematology
