The researchers concluded that the gene expression profiles show that ALLs possessing a rearranged MLL have a highly uniform and distinct pattern that clearly distinguishes them from conventional ALL or acute myelogenous leukemia and warrant designation as the distinct leukemia MLL.
The researchers also found clues about the origin of MLL from the identity of genes that were underexpressed or highly expressed. The underexpressed genes included many important for early development of blood cells. And the overexpressed genes included members of a family known as HOX genes, some of which are regulated by the MLL gene.
When we look at these patterns of gene expression and also at the cells of origin of MLL, we see a pattern indicating that they are very early lymphoid progenitor cells, said Korsmeyer. This suggests that MLL is caused by arrested maturation of lymphocytes. Once we saw that these cells were nothing like those in ALL, we understood why these children dont respond well at all to standard chemotherapy for ALL, he said.
When the scientists compared the genes whose expression is most characteristic of ALL, MLL and AML, they found patterns distinctive enough to be used to distinguish the three leukemias.
According to Korsmeyer, this study appears to represent the first time that a whole-genome profile has revealed that a chromosome translocation can switch on a specific gene expression program.
A central question with respect to these chromosomal translocations is whether they represent simply an oncogenic cancer hit that will be followed by additional mutations which dictate whether the cancer becomes a conventional ALL or immature infant leukemia, h
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
3-Dec-2001