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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

Item Type:Article
Title:Pre-pre-B acute lymphoblastic leukemia: high frequency of alternatively spliced ALL1-AF4 transcripts and absence of minimal residual disease during complete remission
Creators Name:Janssen, J.W. and Ludwig, W.D. and Borkhardt, A. and Spadinger, U. and Rieder, H. and Fonatsch, C. and Hossfeld, D.K. and Harbott, J. and Schulz, A.S. and Repp, R. and Sykora, K.W. and Hoelzer, D. and Bartram, C.R.
Abstract: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.
Keywords:Base Sequence, Burkitt Lymphoma, Neoplasm DNA, DNA-Binding Proteins, Exons, Gene Rearrangement, Immunophenotyping, Molecular Sequence Data, Myeloid-Lymphoid Leukemia Protein, Neoplasm Proteins, Residual Neoplasm, Nuclear Proteins, Fusion Oncogene Proteins, Polymerase Chain Reaction, Proto-Oncogenes, Remission Induction, Transcription Factors
Source:Blood
ISSN:0006-4971
Publisher:American Society of Hematology (U.S.A.)
Volume:84
Number:11
Page Range:3835-3842
Date:1 December 1994
Official Publication:http://bloodjournal.hematologylibrary.org/cgi/content/abstract/84/11/3835
PubMed:View item in PubMed

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