Recently, we identified the YEATS domain of AF9 (ALL1 fused gene from chromosome 9) as a novel acetyl-lysine-binding module and showed that the ENL (eleven-nineteen leukemia) YEATS domain is an essential acetyl-histone reader in acute myeloid leukemias.
Further, there were evident differences between the expression profiles of AMLs in which ALL-1 had undergone fusion to other genes and AMLs with partial duplication of ALL-1.
Karyotyping detected abnormal chromosome 11 only in 4/43 patients and Classical t(4:11) in one AML patient but combination of Painting FISH and LS-FISH confirmed ALL-1 gene alteration in 17/18 cases.
Moreover, although the ALL1 fusion transcripts seen in AML always maintain the open reading frame, the open reading frame was preserved in only 5 of 10 fusion transcripts from normal donors.
11q23 translocations (t(11q23)) are recurring cytogenetic abnormalities in both acute myeloid leukemia (AML) and acute lymphoblastic leukemia, involving the same gene, ALL1 (or MLL).
The partial tandem duplication of the ALL1 (MLL) gene has been found in several such cases of AML, yet its frequency and clinical significance are unclear.
DNA sequencing in the region disclosed the presence of AF-6, a gene that had been identified as the ALL-1 fusion partner involved in acute myeloid leukemias with t(6;11)(q27;q23) translocations.
We report here the cellular localization of the HRX/ALL1 protein as well as that of the HRX/ALL1-eps15 fusion protein, the result of the t(1;11) (p32-q23) translocation of acute myeloid leukemias.
We conclude that the partial tandem duplication of ALL1 is present in most, if not all, cases of AML with +11 as a sole abnormality, and can be found in cases of AML with +11 or +11q accompanied by other cytogenic abnormalities.
The association of IgH rearrangements with ALL-1 alterations in AML, coupled to the frequent detection in this subset of lymphoid associated markers, further supports the origin of these tumors from a common multipotent precursor with bipotential lymphoid and monocytic differentiation capability.
We conclude that molecular rearrangement of ALL-1 often can be detected in de novo AML, despite the absence of cytogenetic abnormalities involving 11q23.
We have recently reported the detection by Southern blot of ALL-1 gene rearrangements in adult patients with acute myeloid leukemia lacking cytogenetic evidence of 11q23 translocations.
We have previously reported the detection of ALL-1 gene rearrangements in adult patients with acute myeloid leukemia lacking cytogenetic evidence of 11q23 translocations.
Using an 859-base pair BamHI fragment of human ALL-1 complementary DNA that recognizes the genomic breakpoint region for de novo ALL and AML, we investigated two cases of secondary AML that followed etoposide-treated primary B-lineage ALL.