Ents, Gene expression profiling, Protein kinases, Cellular pathwaysBackground Chronic myeloid leukemia (CML) can be a myeloproliferative disorder derived from hematopoietic stem cell transformation and characterized by heterogeneous biological and clinical features. The CML molecular marker is BCR/ABL1 fusion gene generation as a consequence of a reciprocal t(9;22)(q34;q11) [1,2]. In most circumstances, the Philadelphia (Ph) chromosome is cytogenetically detectable but about 50 of CML individuals show variant t (9;22)(q34;q11) rearrangements with all the involvement of more chromosomes [3,4]. In these cases the BCR/ ABL1 fusion gene is often revealed by Fluorescence in situ hybridization (FISH) or reverse transcriptasepolymerase chain reaction [5]. The occurrence of genomic microdeletions proximally to ABL1 or distally to Correspondence: [email protected] Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology Section University of Bari, 70124, Bari, ItalyBCR has been reported in CML situations with variant translocations using a greater frequency (3040 ) than in situations with classic t(9;22) (1018 ) [6,7]. The prognostic significance of variant t(9;22) was unclear and debated inside the preimatinib era, whereas recent studies of big CML series have reported that the presence of variant translocations has no effect on the cytogenetic and molecular response or on prognosis [6,8]. However, the molecular bases of biological variations involving CML individuals with classic and variant t(9;22) have never ever been elucidated. Within this study, we performed gene expression profiling (GEP) by microarrays to recognize a signature discriminating CML individuals bearing variant rearrangements from those with classic t(9;22)(q34;q11). A list of 59 genes was discovered to be significantly associated with the two analyzed groups showing a differential expression. We applied network evaluation to evaluate potential pathways2013 Albano et al.; licensee BioMed Central Ltd. This can be an Open Access report distributed below the terms on the Inventive Commons Attribution License (http://creativecommons.Buy1359656-11-3 org/licenses/by/2.1259509-27-7 Chemscene 0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original perform is properly cited.PMID:24377291 Albano et al. Molecular Cancer 2013, 12:36 http://www.molecularcancer.com/content/12/1/Page 2 ofFigure 1 Hierarchical genes clustering in CML with classic (12 situations) and variant (8 circumstances) t(9;22) displaying a 59gene signature. Each row represents a single gene; green indicates differentially decreased expression of each gene in CML patient samples with variant t(9;22) compared with classic t(9;22) and red indicates differentially enhanced expression. The far more saturated the color, the greater the degree of differential expression. N/A indicates genomic sequences not yet annotated.involved in CML heterogeneity. An general deregulation of genes encoding for protein kinases and involved in crucial cellular pathways which include MAPK (mitogenactivated protein kinase) signaling was discovered, unveiling the biological basis of differences in the CML individuals subgroup with variant rearrangements.Findings Banding and molecular cytogenetic analyses permitted the identifications of 12 CML instances with classic t(9;22) and eight circumstances with variant translocations (Further file 1, Additional file 2). The BCR/ABL1 fusion evaluation revealed the occurrence of b2a2 or b3a2 junctions in 10 (7 with classicAlbano et al. Molecular Cancer 2013, 12:36 http://www.molecularcancer.