Elevated MLF1 expression correlates with malignant progression from myelodysplastic syndrome

MLF1 is a novel protein identified as the NPM-MLF1 chimeric protein produce d by a t(3;5)(q25.1;q34) chromosomal translocation, which is associated wit h myelodysplastic syndrome (MDS), often prior to acute myeloid leukemia (AM L), except for M3. The clinical features of t(3;5)-positive myeloid disorde rs suggest that this chimeric protein is involved in dysregulation of proge nitor cells with the capability to differentiate into multiple lineages. So far, involvement of wild-type MLF1 in hematopoiesis or in leukemogenesis h as not been fully investigated. In the present study, 65 patients with AML and 44 patients with MDS were tested for the expression of MLF1 using the q uantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method . A significantly higher level of MLF1 expression (ratio of MLF1/beta-actin mRNA >0.4) was readily detected in seven of 65 patients with de novo AML, three of 12 with post-MDS AML and seven of 44 with MDS, but not in any pati ents with ALL (n =18). According to the FAB classification, high levels of MLF1 were found in patients with relatively immature subtypes of AML (M1, M 2, M6 and M7) and high risk MDS (RAEB and RAEB-T). These findings indicate that the pattern of MLF1 expression is identical to the clinical morphology appearing in the t(3;5)-positive myeloid disorders and is correlated to th e MDS-associated AML and transformation phase of MDS in t(3;5)-negative mye loid disorders. A CD34(+) population of normal bone marrow cells preferenti ally expressed MLF1 with obviously decreasing levels of expression during m aturation. Therefore, MLF1 normally functions in multi-potent progenitor ce lls and its dysregulation may take part in leukemogenesis from MDS.