Breakpoints at 11q23 in infant leukemias with the t(11;19)(q23;p13) are clustered

Abstract

We have analyzed a series of nine infant leukemias that carry a t(11;19)(q23;p13). They had the morphologic features of acute lymphoblastic leukemia (ALL) and expressed markers typical of B-cell progenitor ALL or pre-B ALL; one coexpressed myeloid markers in addition to lymphoid markers (biphenotypic). Two probes (P/S4 and 98.40) subcloned from a yeast artificial chromosome (YAC) known to span the breakpoint in the t(4;11) were used to investigate DNA isolated from the leukemic cells of these patients. A total of approximately 15 kb of genomic DNA in the vicinity of the probes was examined by conventional Southern blot analysis using a series of restriction enzymes. In eight of the nine cases, the breakpoint could be mapped to an approximately 10-kb BamHI fragment disclosed by hybridization to the P/S4 probe.

Investigation of Minimal Residual Disease in Childhood and Adult Acute Lymphoblastic Leukaemia by Molecular Analysis

“…The MLL gene is usually rearranged in these cases and the most common chromosomal partner site is 4q21, the site of the AF4/FEL gene (Gu et al , 1992; Kearney et al , 1992; Tkachuk et al , 1992) in the translocation t(4;11)(q21;q23). Southern analyses have demonstrated that breakpoints in different individuals and from different translocations cluster within a region <5.8 kb in length (Chen et al , 1991; Morgan et al , 1992). Molecular analysis of presentation material has demonstrated a higher incidence of rearrangement than detected by cytogenetic analysis.…”

Tumorigenesis in mice with a fusion of the leukaemia oncogene Mll and the bacterial lacZ gene

“…Chromosome 11q23 is important as translocations occur here in both acute myeloid and lymphoblastic leukaemias (Rowley, 1993; Bernard and Berger, 1995; Rubnitz et al ., 1996; Look, 1997; Gilliland, 1998) as well as in therapy‐related leukaemias (DeVore et al ., 1989; Pui et al ., 1989; Cimino et al ., 1997; Nasr et al ., 1997; Rowley et al ., 1997; Sobulo et al ., 1997; Atlas et al ., 1998; Felix, 1998). Molecular cloning of various translocation breakpoints revealed a gene called MLL (also called ALL‐1 , HRX or HTRX ) in which the translocations occur (Ziemin‐van der Poel et al ., 1991; Djabali et al ., 1992; Gu et al ., 1992; Morgan et al ., 1992; Tkachuk et al ., 1992; Thirman et al ., 1993). The affected region of the MLL gene is fairly small, around exon 8, but the chromosomal translocations result in fusion with a range of genes from other chromosomes.…”

Multiple clonal MLL fusions in a patient receiving CHOP‐based chemotherapy

“…The majority of MLL breakpoints associated with clinical disease are found within an 8·3 kbp tract of MLL defined by BamH1 restriction sites that includes MLL exons 8–14 (Morgan et al , ; Thirman et al , ). Of note, those MLL fusions genes linked to both infant acute leukaemia (IAL) and therapy‐related acute myeloid leukamia (tAML) have their breakpoints primarily located in the 3′ region of the break cluster region (BCR) (Broeker et al , ; Cimino et al , ).…”