title: Analysis of Ikaros family splicing variants in human hematopoietic lineages.
abstract: Transcription factors from the Ikaros family are involved in lymphocyte differentiation and have a critical role at specific check points of the haemopoietic pathway. However, how developmentally regulated changes are reflected in gene expression programs of lymphocyte differentiation is not well understood. It has been suggested that disregulation of transcription factors from the Ikaros family is associated with the development of different human leukemias. In this work we analyzed the state of Ikaros family members in different leukemic cells with the aim to explore the transcriptional control of human hematopoietic lineages and shed some new light on our understanding of transcription factor significance in human leukemias. By means of RT-PCR and specific primers we investigated the expression of Ikaros, Aiolos and Helios transcription factors and their splicing variants in seven leukemia cell lines derived from different types of leukemia (ALL, CML, AML) and lymphoma (histiocytic lymphoma, Burkitt lymphoma and anaplastic large cell lymphoma). In all of the cell lines examined Ikaros was present in dominant Ik1 to Ik4 isoforms and small Ik6 isoform was absent. Aiolos was expressed in the majority of the cell lines, of both, B and T origin, in the form of the full length Aio1. Helios was also present only in two long isoforms Hel1 and Hel2, and was absent in one third of the lines. Similar distribution of positive and negative expression of Aiolos and Helios found in various types of leukemias could implicate common pathways of their regulation.
authors.affiliation: Department of Molecular Biology, Faculty of Science, Zagreb, Croatia.
authors.forename: Maja
authors.initials: M
authors.lastname: Matulić
authors.forename: Mladen
authors.initials: M
authors.lastname: Paradzik
authors.forename: Biljana Jelić
authors.initials: BJ
authors.lastname: Puskarić
authors.forename: Jagoda
authors.initials: J
authors.lastname: Stipić
authors.forename: Mariastefania
authors.initials: M
authors.lastname: Antica
mesh_terms: D017398:Alternative Splicing; D002051:Burkitt Lymphoma / Q000235:genetics / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic; D015972:Gene Expression Regulation, Neoplastic; D018922:HL-60 Cells; D019337:Hematologic Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics*; D019169:Jurkat Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000473:pathology; D017728:Lymphoma, Large-Cell, Anaplastic / Q000235:genetics / Q000473:pathology; D005810:Multigene Family / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020298:U937 Cells
chemical_list: C497239:IKZF1 protein, human; C111431:IKZF2 protein, human; C106285:IKZF3 protein, human; D051740:Ikaros Transcription Factor