BACKGROUND: AF-4 is a common partner gene of MLL. AF-4 breakpoints occur in introns, but most AF-4 introns are uncharacterized. METHODS AND RESULTS: We cloned AF-4 intron 4 and examined the frequency of breakpoints in this intron. The 5.8-kb intron is rich in repeat sequences and was the site of translocation in 3 of 17 leukemias with t(4;11). We cloned the der (11) and der (4) breakpoints and isolated the fusion transcripts in the cell line MV4-11 and in a de novo acute lymphoblastic leukemia (ALL). Both translocations joined MLL intron 6 and AF-4 intron 4. In MV4-11, 249 bases from AF-4 were present in both derivative chromosomes, indicating duplication. In the de novo ALL, duplication of 446 bases from MLL and AF-4 occurred. Reciprocal fusion transcripts were expressed. CONCLUSIONS: Intronic sequence of AF-4 is useful for molecular diagnosis of t(4;11). Duplicated intronic regions suggest staggered chromosomal breakage.
BACKGROUND:AF-4 is a common partner gene of MLL. AF-4 breakpoints occur in introns, but most AF-4 introns are uncharacterized. METHODS AND RESULTS: We cloned AF-4 intron 4 and examined the frequency of breakpoints in this intron. The 5.8-kb intron is rich in repeat sequences and was the site of translocation in 3 of 17 leukemias with t(4;11). We cloned the der (11) and der (4) breakpoints and isolated the fusion transcripts in the cell line MV4-11 and in a de novo acute lymphoblastic leukemia (ALL). Both translocations joined MLL intron 6 and AF-4 intron 4. In MV4-11, 249 bases from AF-4 were present in both derivative chromosomes, indicating duplication. In the de novo ALL, duplication of 446 bases from MLL and AF-4 occurred. Reciprocal fusion transcripts were expressed. CONCLUSIONS: Intronic sequence of AF-4 is useful for molecular diagnosis of t(4;11). Duplicated intronic regions suggest staggered chromosomal breakage.
Authors: M D Megonigal; N K Cheung; E F Rappaport; P C Nowell; R B Wilson; D H Jones; K Addya; D G Leonard; B H Kushner; T M Williams; B J Lange; C A Felix Journal: Proc Natl Acad Sci U S A Date: 2000-03-14 Impact factor: 11.205
Authors: B D Lovett; L Lo Nigro; E F Rappaport; I A Blair; N Osheroff; N Zheng; M D Megonigal; W R Williams; P C Nowell; C A Felix Journal: Proc Natl Acad Sci U S A Date: 2001-08-07 Impact factor: 11.205
Authors: M D Megonigal; E F Rappaport; R B Wilson; D H Jones; J A Whitlock; J A Ortega; D J Slater; P C Nowell; C A Felix Journal: Proc Natl Acad Sci U S A Date: 2000-08-15 Impact factor: 11.205
Authors: Leslie J Raffini; Diana J Slater; Eric F Rappaport; Luca Lo Nigro; Nai-Kong V Cheung; Jaclyn A Biegel; Peter C Nowell; Beverly J Lange; Carolyn A Felix Journal: Proc Natl Acad Sci U S A Date: 2002-04-02 Impact factor: 11.205