Micro RNA (miRNA) is a recently discovered class of transcription regulators. Its role in normal and malignant transformation has been extensively investigated. It is emerging that miRNA expression profiling may be a useful tool for diagnostic and prognostic purposes; however, only a limited number of studies have shown direct involvement of miRNA genes in malignant transformation. There are examples of the role of miRNA in the pathogenesis of B-cell lymphoid malignancies: expression of miR-155, miR-221 and miR-21 can distinguish between the activated B-cell phenotype and germinal center phenotype of diffuse large B-cell lymphoma; the miR-15a/miR-16-1 cluster, located on 13q14, is deleted in chronic lymphocytic leukemia (CLL). 1, 2 In myeloid disorders, a recurrent translocation, t (2; 11)(p21; q24), has been shown to activate the miR-125b-1 on chromosome 11, which potentially defines a specific disease subtype. 3 A second locus containing miR-125b-2 is located on 21q21; chromosome 21 is frequently duplicated or rearranged in human hematological malignancies. In B-cell lymphoid malignancies, chromosomal translocations affecting the immunoglobulin heavy chain locus (IGH@) are known to result in the transcriptional activation of a partner gene and to represent an important step in cellular transformation. Recently, a number of novel chromosomal breakpoints have uncovered previously unknown B-cell oncogenes. We now report the transcriptional activation of miR-125b-1 in the recurrent translocation, t (11; 14)(q24; q32), involving IGH@ in B-cell precursor acute lymphoblastic leukemia (BCP-ALL), thereby extending the involvement of miR-125b-1 to lymphoid precursor transformation.

Two adult BCP-ALL patients with t (11; 14)(q24; q32) were identified from the Groupe Francophone de Cytogénétique Hématologique (GFCH)(P1) and the Leukaemia Research UK Cancer Cytogenetics Group Karyotype Database in Acute Leukaemia (P2). The 28 BCP-ALL patients without t (11; 14) were collected by the Service d’Hématologie Biologique, Groupe Hospitalier Pitié-Salpêtriere, Paris, France and the Laboratoire de Biochimie Génétique, Hôpital Robert Debré, Paris, France. Samples were obtained with informed consent in accordance with the Declaration of Helsinki. Conventional cytogenetic analysis was performed on diagnostic bone marrow samples using standard procedures. Fluorescence in situ hybridization (FISH) was carried out on the same diagnostic samples. The involvement of IGH@ was confirmed using the commercial LSI IGH dual-color break-apart rearrangement probe (Abbott Diagnostics, Rungis, France). A break-apart probe was designed to identify the involvement of miR-125b-1 in the translocation using bacterial artificial chromosome (BAC) clones RP11-164B14 and RP11-419A21 (Supplementary Figure 1). The region of miR-125b-2 on 21q21 was analyzed with BAC clones RP11-10E12, RP11-165H8 and RP11-1051B20. Long-distance inverse PCR (LDI-PCR) from IGHJ was performed as previously described. Sequences were analyzed locally or at http://genome. ucsc. edu/(human genome build hg18). Total RNA was extracted using standard methods. Reverse transcriptase-PCR (RT-PCR) was performed for each