Leukemia is a neoplastic proliferation of cells of hematopoietic origin that arises following somatic mutation in a single hematopoietic stem cell, the progeny of which forms a clone of leukemia cells. Genetic alterations leading to leukemia transformation of a cell are often associated with major alterations of chromosomes that can be detected by studying cells of the leukemic clone in mitosis. One of these alterations is a chromosomal translocation that is often used to identify genes potentially involved in other type of rearrangements such as deletions. Abnormalities of chromosome band 13q14 occur in hematologic malignancies of all lineages and at all stages of differentiation. Unlike other chromosomal translocations, which are usually specific for a given lineage, the chromosomal translocation t(12;13)(p12;q14) has been observed in both B-cell and T-cell precursor acute lymphoblastic leukemia (ALL), in differentiated and undifferentiated acute myeloid leukemia (AML) and in chronic myeloid leukemia at progression to blast crisis (CML-BC). Recently, we have shown the presence of a myeloid- and lymphoid-specific breakpoint cluster regions within chromosome band 13q14 in acute leukemia (Genes Chromosome Cancer 25:222-229,1999). In addition, a new cell line has been established from one of the lymphoid cases, MUTZ5, that carries a single t(12;13) translocation (

Leukemia
15
:
1471
-1474,
2001
). The molecular characterization of this translocation led to the identification of a new gene, FLJ13639, that is disrupted and lost in the MUTZ5 cell line. This gene shares homologies with the large family of short-chain dehydrogenase reductase (SDR). Furthermore, three transcripts and proteins were found to be differentially expressed for this gene, where P1 is potentially the active form of dehydrogenase, while P2 and P3 are lacking the co-activator site. We previously reported that one of the consequences of the loss of FLJ13639 is the over-expression of CD24 that appears to provide leukemia cells with a proliferation and invasiveness advantage, as well as a certain degree of chemoresistance. In addition, data on patient samples indicated a correlation between survival and CD24High/FLJ/P1Low expression profile (Blood 106 (11), Nov 2005). We show that FLJ/P1 is a new mitochondrial protein that is important for the respiration and apoptosis processes. Restoration of the FLJ/P1 function induced CD24 down-regulation, decreased invasive potential as assessed by Matrigel assay and decreased chemoresistance. FLJ/P1 function restoration might represent a new potential therapy, that could, when combined with the assessment of FLJ/P1-CD234 expression profiles, allow the future development of personalized treatment.

Topics:
apoptosis, mitochondria, oxidoreductase, respiration, leukemia, acute lymphocytic leukemia, blast phase, cancer, hematologic neoplasms, leukemia, acute

Disclosure: No relevant conflicts of interest to declare.

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2006, The American Society of Hematology
2006
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