Clinical and Translational Oncology

, Volume 20, Issue 4, pp 542–549 | Cite as

Expression differences of genes in the PI3K/AKT, WNT/b-catenin, SHH, NOTCH and MAPK signaling pathways in CD34+ hematopoietic cells obtained from chronic phase patients with chronic myeloid leukemia and from healthy controls

  • R. de Cássia Viu Carrara
  • A. M. Fontes
  • K. J. Abraham
  • M. D. Orellana
  • S. K. Haddad
  • P. V. B. Palma
  • R. A. Panepucci
  • M. A. Zago
  • D. T. Covas
Research Article

Abstract

Purpose

The fusion gene BCR-ABL has an important role to the progression of chronic myeloid leukemia (CML) and several signaling pathways have been characterized as responsible for the terminal blastic phase (BP). However, the initial phase, the chronic phase (CP), is long lasting and there is much yet to be understood about the critical role of BCR-ABL in this phase. This study aims to evaluate transcriptional deregulation in CD34+ hematopoietic cells (CD34+ cells) from patients with untreated newly diagnosed CML compared with CD34+HC from healthy controls.

Methods

Gene expression profiling in CML-CD34 cells and CD34 cells from healthy controls were used for this purpose with emphasis on five main pathways important for enhanced proliferation/survival, enhanced self-renewal and block of myeloid differentiation.

Results

We found 835 genes with changed expression levels (fold change ≥ ±2) in CML-CD34 cells compared with CD34 cells. These include genes belonging to PI3K/AKT, WNT/b-catenin, SHH, NOTCH and MAPK signaling pathways. Four of these pathways converge to MYC activation. We also identified five transcripts upregulated in CD34-CML patients named OSBPL9, MEK2, p90RSK, TCF4 and FZD7 that can be potential biomarkers in CD34-CML-CP.

Conclusion

We show several mRNAs up- or downregulated in CD34-CML during the chronic phase.

Keywords

Chronic myeloid leukemia CD34+ cells BCR-ABL Gene expression Chronic phase microRNA 

Notes

Compliance with ethical standards

Conflict of interest

There are no conflicts of interest.

Human participants

All procedures performed in studies involving human participants were in accordance with the ethical standards of the FMRP-USP Hospital and with the 1964 Helsinki declaration and its later amendments.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2017

Authors and Affiliations

  1. 1.Center for Cell-Based Therapy of the Regional Blood Center of Ribeirão PretoRibeirao PretoBrazil
  2. 2.UNAERPRibeirao PretoBrazil
  3. 3.Department of Genetics, Medical School of Ribeirão PretoUniversity of São PauloRibeirao PretoBrazil
  4. 4.Department of Puericulture and Pediatrics, Medical School of Ribeirão PretoUniversity of São PauloRibeirao PretoBrazil
  5. 5.Department of Clinical Medicine, Medical School of Ribeirão PretoUniversity of São PauloRibeirao PretoBrazil

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