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Pre-pre-B acute lymphoblastic leukemia: high frequency of alternatively
spliced ALL1-AF4 transcripts and absence of minimal residual disease during
complete remission
JW Janssen, WD Ludwig, A Borkhardt, U Spadinger, H Rieder, C Fonatsch, DK Hossfeld, J Harbott, AS Schulz and R Repp
Department of Pediatrics II, University of Ulm, Germany.
We used the polymerase chain reaction (PCR) to detect ALL1-AF4
rearrangements, the molecular hallmark of t(4;11) in a series of 46 pre-
pre-B (CD19+, CD24+, CD10/CD20/cylgM/sIgM-) acute lymphoblastic leukemias
(ALL). Eighteen patients (39%) exhibited fusion transcripts including 4 of
12 children and 14 of 34 adults. This genetic defect was associated with
hyperleukocytosis (median leukocyte count 176 x 10(9)/L) and expression of
myeloid-associated antigens (CDw65+). In contrast, only two patients from a
group of 67 common (CD19/CD10+, cylgM/sIgM-) and pre-B ALLs (CD19/cylgM+,
CD10 +/-, sIgM-) showed ALL1- AF4 mRNA. All PCR-positive cases showed
multiple amplification products representing alternative splicing events.
Moreover, reciprocal der (4)- derived AF4-ALL1 transcripts were observed in
65% of the cases analyzed. Eight of the 18 pre-pre-B ALL patients with an
ALL1-AF4 recombination are currently in complete continuous remission for
up to 54 months (median, 26 months). Twelve remission samples were
available from seven cases, and all of them lacked evidence of minimal
residual disease. Overall this study documents a similarly high incidence
of ALL1-AF4 recombinations in children (infants excluded) and adults with
pre-pre-B ALL and demonstrates the decline of the leukemic cell clone below
the detection level of PCR in a remarkable proportion of patients under
intense treatment protocols.
Volume 84,
Issue 11,
pp. 3835-3842,
12/01/1994
Copyright © 1994 by The American Society of Hematology
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