Molecular and cellular bases of chronic myeloid leukemia

Chen, Yaoyu; Peng, Cong; Li, Dongguang; Li, Shaoguang

doi:10.1007/s13238-010-0016-z

Cited by 60 publications

(40 citation statements)

References 77 publications

(87 reference statements)

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“…The hallmark genetic abnormality of chronic myelogenous leukaemia (CML) is the 'Philadelphia chromosome', small chromosome resultant of a t(9;22)(q34;q11) translocation, which resulted the chimeric gene BCR-ABL1 (Chen et al 2010;Ren, 2005). Imatinib, a potent inhibitor of the oncogenic tyrosine kinase BCR-ABL, has shown remarkable clinical activity in patients with CML.…”

Section: Discussionmentioning

confidence: 99%

4-Nerolidylcatechol analogues as promising anticancer agents

Cortez

Ávila

Cunha

et al. 2015

European Journal of Pharmacology

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4-Nerolidylcatechol (1) is an isolated compound from Pothomorphe umbellata L. (Piperaceae) with promising antitumor cells properties. However it presents lability under light and room temperatures. Many efforts have been directed towards discovering anticancer agents endowed with cytotoxic activities. Here, we evaluated cytotoxic effects of 4-NRC analogues (LQFMs 2-6) and the cell death pathways induced by these compounds in multidrug-resistant K562 cells. Compounds (2-6) exhibited cytotoxic activities in a concentration-dependent manner against leukaemic cells, specially the compounds (3) and (5). Additionally, compounds (1), (3) and (5) promoted marked alterations on the cell morphology, including nuclear changes as demonstrated by Hoescht 33342 staining. Moreover, these compounds promoted apoptosis induction in K562 cells by phosphatidylserine exposure, increase of sub-G1 cells and modulation of the caspases-3/7, -8 and -9 activation. In addition, the pancaspase inhibitor z-VAD-fmk partially reduced the apoptosis induced by the compounds (1) and (5)-induced, suggesting caspase-dependent and caspase-independent cell death pathways. Compounds (1) and (5) also modified the cell cycle progression by G0/G1 and S arrest, respectively. Furthermore, compounds (1), (3) and (5) promoted mitochondrial dysfunction associated to accumulation of cytosolic cytochrome c and modulated the NF-ĸB activation. In addition, unlike their analogues, 4-NRC (1) also promoted a significant cyclin D1 inhibition. Together, these data suggest that the mechanism of cell death of 4-NRC and its analogues (3) and (5) occurs by apoptosis through mitochondrial mechanisms. Considering that LQFMs are biocompatible synthetic analogues produced by molecular simplification of (1) without the chiral centre, which is associated with the instability found in compound (1), we suggest that these compounds are promising candidates for further pre-clinical studies.

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Section: Discussionmentioning

confidence: 99%

4-Nerolidylcatechol analogues as promising anticancer agents

Cortez

Ávila

Cunha

et al. 2015

European Journal of Pharmacology

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“…These data suggest that the blastic phase may be the product of genetic alterations inside the progenitor hematopoietic cell lineage, which gives self-renewal properties [34][35][36].…”

Section: Molecular Biologymentioning

confidence: 90%

Mexican Guidelines for the Diagnosis and Treatment of Chronic Myeloid Leukaemia

Cervera¹,

Godínez²,

Sosa³

et al. 2013

JCT

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Background: This document includes recommendations and guidelines issued by a group of Mexican researchers and specialists gathered in the First National Colloquium for the Diagnosis and Management of Chronic Myeloid Leukaemia (CML) by initiative of Instituto Nacional de Cancerología and with the support of the Leukaemia Department of the MD Anderson Cancer Center. Mexico lacks of updated information taken from its own reality on the diagnosis and treatment of CML and other haematological disorders; besides, there are no national guidelines. Aim: To publish a consensus document with guidelines for the management of CML adjusted to the national environment and overall characteristics. Method: The participants answered a DELPHI questionnaire about the overall aspects of the disease, aiming to target controversial topics, discuss them in the colloquium, and to agree on the best ones. After those meetings, a final document was drawn up. Results: The group presents recommendations for definition, diagnosis, prognosis, monitoring, and treatment of CML in Mexico. Conclusions: Having consensus guidelines for the clinical management of CML in our country will enable the consensual practice of Mexican specialists regarding the clinical approach to CML, as well as optimize the resources which allow the rational planning of the medical care strategies.

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“…TKIs induce remissions in the large majority of patients with CML, but LSCs themselves are resistant to TKIs (19). We and others have described regulatory pathways that modify development of CML, and the growth and differentiation properties of LSCs.…”

Section: Prkd2 Is An Essential and Direct Target Of Gabp In Hscsmentioning

confidence: 91%

GABP transcription factor is required for development of chronic myelogenous leukemia via its control of PRKD2

Yang

Zhang

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Hematopoietic stem cells (HSCs) are the source of all blood lineages, and HSCs must balance quiescence, self-renewal, and differentiation to meet lifelong needs for blood cell development. Transformation of HSCs by the breakpoint cluster region-ABL tyrosine kinase (BCR-ABL) oncogene causes chronic myelogenous leukemia (CML). The E-twenty six (ets) transcription factor GA binding protein (GABP) is a tetrameric transcription factor complex that contains GABPα and GABPβ proteins. Deletion in bone marrow of Gabpa , the gene that encodes the DNA-binding component, caused cell cycle arrest in HSCs and profound loss of hematopoietic progenitor cells. Loss of Gabpα prevented development of CML, although mice continued to generate BCR-ABL–expressing Gabpα-null cells for months that were serially transplantable and contributed to all lineages in secondary recipients. A bioinformatic screen identified the serine-threonine kinase protein kinase D2 (PRKD2) as a potential effector of GABP in HSCs. Prkd2 expression was markedly reduced in Gabpα-null HSCs and progenitor cells. Reduced expression of PRKD2 or pharmacologic inhibition decreased cell cycling, and PRKD2 rescued growth of Gabpα-null BCR-ABL–expressing cells. Thus, GABP is required for HSC cell cycle entry and CML development through its control of PRKD2. This offers a potential therapeutic target in leukemia.

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Molecular and cellular bases of chronic myeloid leukemia

Cited by 60 publications

References 77 publications

4-Nerolidylcatechol analogues as promising anticancer agents

4-Nerolidylcatechol analogues as promising anticancer agents

Mexican Guidelines for the Diagnosis and Treatment of Chronic Myeloid Leukaemia

GABP transcription factor is required for development of chronic myelogenous leukemia via its control of PRKD2

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