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Pérez Jiménez Mario

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Péret Jiménez Mario
The hierarchical structure of the hematopoietic system can explain chronic myeloid leukaemia progression.

Aug 28 - szerda

13:30 – 15:30

II. Poszterszekció

P41

The hierarchical structure of the hematopoietic system can explain chronic myeloid leukaemia progression.

Pérez Jiménez Mario¹, Derényi Imre² and Szöllősi Gergely³

¹ Eötvös Loránd University, Department of Biological Physics

² Department of Biological Physics, ELTE-MTA ‘Lendulet’ Biophysics Research Group

³ Department of Biological Physics, ELTE-MTA ‘Lendulet’ Evolutionary Genomics.

Chronic myeloid leukaemia (CML) is one of the most studied and well-known cancer types. It was the first known human cancer that can be initiated by a single chromosomal abnormality, this translocation is known as the BCR-ABL1 fusion gene [1]. CML progression is divided into three phases, these can be distinguished with a bone marrow biopsy or a blood smear test. These two methods provide clear criteria for each one of the stages [2].

The initial chronic phase is characterized by a long constant evolution estimated between 5 and 7 years. This initial phase is defined by an increased number of white blood cells (WBC) and the limited presence of immature blasts cells in the blood. Despite the presence of blast cells in the blood, the full spectrum of mature cells is still present. At this point, a cytogenetic analysis will conclude that BCR-ABL1 mutated cells have replaced healthy cells.

Transition to more advanced stages of the disease is characterized by an increased amount of blast cells in the blood (above 20%). Mature cells cannot be found in blood samples anymore. Tumour heterogeneity is also common in advanced phases. Resistance to treatment and unresponsive high WBC count are stereotypic of the final stage of the disease.

A model of hierarchical differentiation [3] is used to simulate the hematopoietic system in silico. We perform simulations about the dynamics of the BCR-ABL1 mutants in a two-compartment system. Terminally differentiated cells can migrate from the bone marrow to the bloodstream in healthy conditions. The chronic phase is in agreement with increased cellularity in the bone marrow and the initial leaking of progenitor cells to the bloodstream. In the simulation, new mutations increase self-renewal and stop the differentiation capacity of cells.

Our results show that CML development can be explained based on the hierarchical structure of blood formation. The model provides a mathematical picture of CML progression, while the simulations provide with a quantitative and accurate description. Our results provide insight about cancer dynamics, from the initial mutation to final irreversible cell growth.

References

[1] Provan, Drew & Gribben, John. (2018). Molecular hematology.

[2] Junia V. Melo & David J. Barnes. Nature Reviews Cancer ,7 441453 (2007).

[3] Derényi Imre & Szöllősi Gergely J. Nature Communications, 8 14545 (2017).