Abstract
A variety of genetic alterations are considered hallmarks of cancer development and progression. The Ikaros gene family, encoding for key transcription factors in hematopoietic development, provides several examples as genetic defects in these genes are associated with the development of different types of leukemia. However, the complex patterns of expression of isoforms in Ikaros family genes has prevented their use as clinical markers.In this study, we propose the use of the expression profiles of the Ikaros isoforms to classify various hematological tumor diseases. We have standardized a quantitative PCR protocol to estimate the expression levels of the Ikaros gene exons. Our analysis reveals that these levels are associated with specific types of leukemia and we have found differences in the levels of expression relative to five interexonic Ikaros regions for all diseases studied. In conclusion, our method has allowed us to precisely discriminate between B-ALL, CLL and MM cases. Differences between the groups of lymphoid and myeloid pathologies were also identified in the same way.
Highlights
The Ikaros family includes five transcription factors (Ikaros, Helios, Aiolos, Eos and Pegasus) with a key role in the regulation of the hematopoietic system by both potentiating and repressing gene expression [1,2,3]
We studied 46 bone marrow samples from patients with different types of hematologic malignancy (15 B Acute Lymphoblastic Leukemia (B-ALL), 14 Acute Myeloid Leukemia, 5 Chronic Myeloid Leukemia (CML), 7 Cronic Lymphoid Leukemia (CLL) and 5 Multiple Myeloma (MM) cases, with an age range between 3 and 90 years old) (Table 1), which were obtained for diagnostic purposes at the Santa Fe de Bogotá Fundation University Hospital (Colombia) (Table 1)
New paradigm and new uses of the Ikaros family In recent years, many of the new discoveries on role of the Ikaros family in the development of hematological cancers were related to dominant negative isoforms and their association with the development of specific pathologies
Summary
The Ikaros family includes five transcription factors (Ikaros, Helios, Aiolos, Eos and Pegasus) with a key role in the regulation of the hematopoietic system by both potentiating and repressing gene expression [1,2,3]. The first four zinc fingers encode for a DNA-binding domain (DBD), whereas the last two encode for a dimerization domain, which allows the binding between isoforms of the family [5]. Several studies have related defects in different members of this family of transcription factors with the development of hematopoietic neoplasms. Studies on these genes revealed the expression of different DN isoforms of Ikaros (Ik-4, Ik-7 and Ik-8), as well as insertions of 60 bp in
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