We report that p53 inactivation in ALL of B cell lineage is restricted to cases carrying a rearrangement of MLL or c-MYC, whereas it is consistently negative in other molecular subgroups.
We have characterized immunophenotypically defined acute lymphoblastic leukemia (ALL) in Egypt for rearrangements of the antigen receptor genes, and correlated this with rearrangements of ALL-1 and the presence of p53 mutations.
We studied 86 newly diagnosed adults entered on an ALL clinical trial to investigate the incidence of MLL gene rearrangements and to determine clinical, morphologic, immunologic and cytogenetic characteristics of such patients.
The chromosomal breakpoints of t(4;11) translocation of acute lymphoblastic leukemia (ALL) have been recently identified at molecular level and shown to involve the AF4 (FEL) gene on chromosome 4 and the ALL-1 (MLL, Hrx) gene on chromosome 11.
The detection of nonidentical IGH rearrangements suggests that the MLL rearrangement took place in a B-cell precursor or hematopoietic stem cell in one twin which was transferred in utero to the other fetus resulting in ALL with an identical aneuploid karyotype in both infants.
MLL (also known as ALL-I, HTRX, or HRX) gene translocations are among the most common chromosomal abnormalities recognized in both B-lineage acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).
Therefore, we studied 45 cases of childhood ALL with abnormalities of chromosome 11q23 for rearrangement of the MLL gene to determine if this feature confers a uniformly poor prognosis.
Thus, in very young children with ALL (but not AML), the rearrangement status of the 11q23/MLL region supersedes age group as a determinant of treatment outcome.
The 3-year overall survival rate for ALL cases with MLL gene rearrangements was 5.3 +/- 5.2 percent, compared with 88.9 +/- 10.5 percent for cases with germline MLL (P=0.0001).
The translocation t(9;11)(p22;q23), which results in the fusion of MLL to AF9, is the most common of the 11q23 chromosomal abnormalities observed in de novo acute myeloid leukemia (AML), in therapy related leukemia (t-AML), and rarely in acute lymphoblastic leukemia (ALL).
MLL is involved in translocations that result in de novo acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), mixed lineage leukemia, and also in therapy AML (t-AML) and therapy ALL (t-ALL) resulting from treatment with DNA topoisomerase II (topo II) targeting drugs.
Infants less than 1 year of age at diagnosis of acute lymphoblastic leukemia (ALL) have a poor prognosis, which has been attributed primarily to a breakpoint in chromosomal band 11q23 or the MLL gene.
Acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) in infants have in common a high incidence of translocations of the MLL gene at chromosome band 11q23.
Although MLL gene rearrangements are generally associated with a dismal outcome in ALL, two distinct subsets with MLL-ENL fusions have an excellent prognosis.
The relatively high frequency of deletion of the D11S2179 marker compared with the D11S1356 marker suggests that ATM is the target gene of the deletion at the 11q23 locus, and that such deletions may play a role in the pathogenesis of ALL.
Reciprocal translocations involving the MLL gene on chromosome band 11q23 have been observed in both acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).
Co-expression of multiple variants of the MLL/AF4 fusion transcript is a common phenomenon in patients with acute lymphoblastic leukemia (ALL) with t(4;11)(q21;q23).
MLL gene rearrangements are associated with coexpression of myeloid- and lymphoid-associated antigens on leukemic blasts and a dismal outcome in acute lymphoblastic leukemia (ALL).
At the extreme end of the risk spectrum, the t(4;11)/MLL-AF4 and t(9;22)/BCR-ABL almost always confer a dire prognosis in both children and adults with ALL, who warrant high-dose chemotherapy and hematopoietic stem cell rescue to sustain or even induce first remission.
The MLL-ENL fusion was not detectable in blood at the time of ALL diagnosis or after 0.7, 2, 8, 10, and 12 months of therapy but was detectable in blood at 16 months (one in 2.3 x 10(4) cells).