Publications by authors named "A Chávez-González"

21 Publications

Understanding the hematopoietic microenvironment in chronic myeloid leukemia: A concise review.

Curr Res Transl Med 2021 May 4;69(3):103295. Epub 2021 May 4.

Laboratorio de Células Troncales Leucémicas, Unidad de Investigación Médica en Enfermedades Oncológicas, CMN Siglo XXI, Instituto Mexicano del Seguro Social, México. Electronic address:

Chronic myeloid leukemia (CML) is a myeloproliferative disease that results from the BCR-ABL gene-induced transformation of a primitive hematopoietic cell. This disease has been extensively studied, and, as a result, a very effective therapy has been developed: the tyrosine kinase inhibitors. Although, there is a significant knowledge about the intrinsic biology of CML cells, alterations in their bone marrow microenvironment are not yet completely understood. In this concise review, we summarized recent findings on the composition and function of the bone marrow microenvironment in CML, and their importance in the progression of the disease and treatment resistance.
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http://dx.doi.org/10.1016/j.retram.2021.103295DOI Listing
May 2021

Increased expression of hypoxia-induced factor 1α mRNA and its related genes in myeloid blood cells from critically ill COVID-19 patients.

Ann Med 2021 12;53(1):197-207

Unidad de Investigación Médica en Enfermedades Endocrinas, UMAE Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico city, Mexico.

Background: COVID-19 counts 46 million people infected and killed more than 1.2 million. Hypoxaemia is one of the main clinical manifestations, especially in severe cases. HIF1α is a master transcription factor involved in the cellular response to oxygen levels. The immunopathogenesis of this severe form of COVID-19 is poorly understood.

Methods: We performed scRNAseq from leukocytes from five critically ill COVID-19 patients and characterized the expression of hypoxia-inducible factor1α and its transcriptionally regulated genes. Also performed metanalysis from the publicly available RNAseq data from COVID-19 bronchoalveolar cells.

Results: Critically-ill COVID-19 patients show a shift towards an immature myeloid profile in peripheral blood cells, including band neutrophils, immature monocytes, metamyelocytes, monocyte-macrophages, monocytoid precursors, and promyelocytes-myelocytes, together with mature monocytes and segmented neutrophils. May be the result of a physiological response known as emergency myelopoiesis. These cellular subsets and bronchoalveolar cells express HIF1α and their transcriptional targets related to inflammation (CXCL8, CXCR1, CXCR2, and CXCR4); virus sensing, (TLR2 and TLR4); and metabolism (SLC2A3, PFKFB3, PGK1, GAPDH and SOD2).

Conclusions: The up-regulation and participation of HIF1α in events such as inflammation, immunometabolism, and TLR make it a potential molecular marker for COVID-19 severity and, interestingly, could represent a potential target for molecular therapy. Key messages Critically ill COVID-19 patients show emergency myelopoiesis. HIF1α and its transcriptionally regulated genes are expressed in immature myeloid cells which could serve as molecular targets. HIF1α and its transcriptionally regulated genes is also expressed in lung cells from critically ill COVID-19 patients which may partially explain the hypoxia related events.
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http://dx.doi.org/10.1080/07853890.2020.1858234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784832PMC
December 2021

Assessment of Cell Cycle in Primitive Chronic Myeloid Leukemia Cells by Flow Cytometry After Coculture with Endothelial Cells.

Methods Mol Biol 2021 ;2174:207-216

Laboratorio de Células Troncales Leucémicas, Unidad de Investigación Médica en Enfermedades Oncológicas, CMN Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, México.

From the knowledge that hematopoiesis does not occur randomly in the bone marrow but is regulated by the different components of the microenvironment, the use of in vitro coculture systems has been used as a powerful tool in the analysis of different processes that are involved in the maintenance of blood cells. In this chapter, we describe a methodological strategy to perform a coculture between primitive hematopoietic cells and endothelial cells to evaluate cell cycle, an aspect of relevant importance in the permanence of primitive leukemic cells.
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http://dx.doi.org/10.1007/978-1-0716-0759-6_13DOI Listing
April 2021

Parthenolide and DMAPT induce cell death in primitive CML cells through reactive oxygen species.

J Cell Mol Med 2018 10 5;22(10):4899-4912. Epub 2018 Aug 5.

Leukemic Stem Cells Lab, Oncology Research Unit, Mexican Institute of Social Security, Oncology Hospital, "Siglo XXI" National Medical Center, Mexico City, Mexico.

Tyrosine kinase inhibitors (TKI) have become a first-line treatment for chronic myeloid leuakemia (CML). TKIs efficiently target bulk CML cells; however, they are unable to eliminate the leukaemic stem cell (LSC) population that causes resistance and relapse in CML patients. In this study, we assessed the effects of parthenolide (PTL) and dimethyl amino parthenolide (DMAPT), two potent inhibitors of LSCs in acute myeloid leukaemia (AML), on CML bulk and CML primitive (CD34 lin ) cells. We found that both agents induced cell death in CML, while having little effect on the equivalent normal hematopoietic cells. PTL and DMAPT caused an increase in reactive oxygen species (ROS) levels and inhibited NF-κB activation. PTL and DMAPT inhibited cell proliferation and induced cell cycle arrest in G and G phases. Furthermore, we found cell cycle inhibition to correlate with down-regulation of cyclin D1 and cyclin A. In summary, our study shows that PTL and DMAPT have a strong inhibitory effect on CML cells. Given that cell cycle arrest was not dependent on ROS induction, we speculate that this effect could be a direct consequence of NF-κB inhibition and if this mechanism was to be evaded, PTL and DMAPT induced cell death would be potentiated.
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http://dx.doi.org/10.1111/jcmm.13755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156390PMC
October 2018

Global gene expression profiles of hematopoietic stem and progenitor cells from patients with chronic myeloid leukemia: the effect of in vitro culture with or without imatinib.

Cancer Med 2017 Dec 13;6(12):2942-2956. Epub 2017 Oct 13.

Oncology Research Unit, Oncology Hospital, National Medical Center, Mexican Institute for Social Security, Mexico City, Mexico.

In this study, we determined the gene expression profiles of bone marrow-derived cell fractions, obtained from normal subjects and Chronic Myeloid Leukemia (CML) patients, that were highly enriched for hematopoietic stem (HSCs) and progenitor (HPCs) cells. Our results indicate that the profiles of CML HSCs and HPCs were closer to that of normal progenitors, whereas normal HSCs showed the most different expression profile of all. We found that the expression profiles of HSCs and HPCs from CML marrow were closer to each other than those of HSCs and HPCs from normal marrow. The major biologic processes dysregulated in CML cells included DNA repair, cell cycle, chromosome condensation, cell adhesion, and the immune response. We also determined the genomic changes in both normal and CML progenitor cells under culture conditions, and found that several genes involved in cell cycle, steroid biosynthesis, and chromosome segregation were upregulated, whereas genes involved in transcription regulation and apoptosis were downregulated. Interestingly, these changes were the same, regardless of the addition of Imatinib (IM) to the culture. Finally, we identified three genes-PIEZO2, RXFP1, and MAMDC2- that are preferentially expressed by CML primitive cells and that encode for cell membrane proteins; thus, they could be used as biomarkers for CML stem cells.
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http://dx.doi.org/10.1002/cam4.1187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5727298PMC
December 2017