Clinical significance of MLL-AF4 fusion transcript expression in the absence of a cytogenetically detectable t(4;11)(q21;q23) chromosomal translocation.

Leukemic cells from bone marrow (BM) of 17 infants and 127 children with newly diagnosed ALL, as well as fetal liver and BM and normal infant BM samples, were analyzed for presence of a t(4;11) translocation using standard cytogenetic techniques and expression of an MLL-AF4 fusion transcript using standard reverse transcriptase-polymerase chain reaction (RT-PCR) assays as well as nested RT-PCR that is 100-fold more sensitive than standard RT-PCR. Overall, 9 of 17 infants and 17 of 127 noninfant pediatric ALL patients were positive for expression of MLL-AF4 fusion transcripts, as determined by standard and/or nested RT-PCR assays. None of the MLL-AF4(+) cases were positive for E2A-PBX1 or BCR-ABL fusion transcript expression. Although 8 of 9 MLL-AF4(+) infants had cytogenetically detectable t(4;11)(q21;q23), 15 of the 17 MLL-AF4(+) noninfants were t(4;11)-. Infants with MLL-AF4(+) ALL had poor outcomes, whereas non-infant MLL-AF4(+)/t(4;11)- patients had favorable outcomes similar to MLL-AF4(-) patients. Notably, MLL-AF4 transcripts also were detected by nested RT-PCR in 4 of 16 fetal BMs, 5 of 13 fetal livers, and 1 of 6 normal infant BMs, but not in any of the 44 remission BM specimens from pediatric ALL patients. Our results provide unprecedented evidence that MLL-AF4 fusion transcripts can be present in normal hematopoietic cells, indicating that their expression is insufficient for leukemic transformation of normal lymphocyte precursors.

Uckun FM ，Herman-Hatten K ，Crotty ML ，Sensel MG ，Sather HN ，Tuel-Ahlgren L ，Sarquis MB ，Bostrom B ，Nachman JB ，Steinherz PG ，Gaynon PS ，Heerema N ... -  《BLOOD》

Molecular analysis of infant acute lymphoblastic leukemia: MLL gene rearrangement and reverse transcriptase-polymerase chain reaction for t(4; 11)(q21; q23).

Hilden JM ，Frestedt JL ，Moore RO ，Heerema NA ，Arthur DC ，Reaman GH ，Kersey JH ... -  《-》

Cryptic splice site activation during RNA processing of MLL/AF4 chimeric transcripts in infants with t(4;11) positive ALL.

Divoky V ，Trka JM ，Watzinger F ，Lion T ... -  《GENE》

Pro-B-cell to pre-B-cell development in B-lineage acute lymphoblastic leukemia expressing the MLL/AF4 fusion protein.

Bertrand FE ，Vogtenhuber C ，Shah N ，LeBien TW ... -  《-》

Serial analysis of MLL-AF4 chimeric message through successful bone marrow transplantation in a patient with t(4;11)-positive infant-ALL.

A 28-month-old girl with acute lymphoblastic leukemia (ALL) showing a t(4;11)(q21;q23) karyotype successfully underwent allogeneic bone marrow transplantation (BMT) at relapse. The chimeric MLL-AF4 message on her bone marrow (BM) specimens, examined by reverse transcriptase-polymerase chain reaction, was detectable at diagnosis, relapse, and just before BMT but became undetectable following BMT. She has since maintained complete remission. This observation suggests that detection of the chimeric message in BM may be useful to predict clinical outcome in patients with t(4;11) ALL.

Tabata Y ，Hibi S ，Maruyama-Tabata H ，Tsunamoto K ，Todo S ，Sawada T ，Okamura T ，Kawa-Ha K ，Imashuku S ... -  《-》