Scientific background: |
MLL(Myeloid/lymphoid or mixed Lineage Leukemia gene),also called MLL1, ALL1 or CXX7, is a
frequent target for recurrent translocations in acute leukemias that may be characterized as acute
myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or mixed lineage (biphenotypic) leukemia
(MLL). The MLL gene encodes a DNA-binding protein that methylates histone H3 lys4 (H3K4) and
positively regulates expression of target genes, including multiple HOX genes. The MLL gene is
mapped on 11q23.3. A leukemogenicMLL fusion protein that activates HOX expression had no effect on
histone methylation, suggesting a distinct mechanism for gene regulation by MLLand MLL fusion
proteins. The MLL gene encodes a large nuclear protein that is required for the maintenance of HOX
gene expression. MLL is cleaved at 2 conserved sites to generate an N-terminal 320-kD fragment
(N320) and a C-terminal 180-kD fragment (C180), which heterodimerize to stabilize the complex and
confer its subnuclear destination. RNA interference-mediated knockdown of taspase-1 in HeLa cells
resulted in the appearance of unprocessed MLL and the loss of proper HOX gene expression. |
References: |
1. Armstrong, S. A., Staunton, J. E., Silverman, L. B., Pieters, R., den Boer, M. L., Minden, M. D.,
Sallan, S. E., Lander, E. S., Golub, T. R., Korsmeyer, S. J. MLL translocations specify a distinct
gene expression profile that distinguishes a unique leukemia. Nature Genet. 30: 41-47, 2002.
2. Bruch, J., Wilda, M., Teigler-Schlegel, A., Harbott, J., Borkhardt, A., Metzler, M. Occurrence of
an MLL/LAF4 fusion gene caused by the insertion ins(11;2)(q23;q11.2q11.2) in an infant with acute
lymphoblastic leukemia. (Letter) Genes Chromosomes Cancer 37: 106-109, 2003.
3. Caligiuri, M. A., Strout, M. P., Oberkircher, A. R., Yu, F., de la Chapelle, A., Bloomfield, C. D. The
partial tandem duplication of ALL1 in acute myeloid leukemia with normal cytogenetics or trisomy 11
is restricted to one chromosome. Proc. Nat. Acad. Sci. 94: 3899-3902, 1997. |