An Overview and Update of Chronic Myeloid Leukemia for Primary Care Physicians

Granatowicz, Austin T.; Piatek, Caroline I.; Moschiano, Elizabeth; El-Hemaidi, Ihab; Armitage, JO; Akhtari, Mojtaba

doi:10.4082/kjfm.2015.36.5.197

Cited by 67 publications

(57 citation statements)

References 38 publications

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“…Chronic myeloid leukemia (CML), with more than 6660 newly diagnosed cases in the United States, is responsible for almost 15% of adult leukemias [52]. CML is associated with the Philadelphia chromosome t(9;22)(q34;q11) and the BCR-ABL1 fusion gene.…”

Section: Mir-144 In Chronic Myeloid Leukemiamentioning

confidence: 99%

MiR-144: A New Possible Therapeutic Target and Diagnostic/Prognostic Tool in Cancers

Kooshkaki

Rezaei

Rahmati

et al. 2020

IJMS

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MicroRNAs (miRNAs) are small and non-coding RNAs that display aberrant expression in the tissue and plasma of cancer patients when tested in comparison to healthy individuals. In past decades, research data proposed that miRNAs could be diagnostic and prognostic biomarkers in cancer patients. It has been confirmed that miRNAs can act either as oncogenes by silencing tumor inhibitors or as tumor suppressors by targeting oncoproteins. MiR-144s are located in the chromosomal region 17q11.2, which is subject to significant damage in many types of cancers. In this review, we assess the involvement of miR-144s in several cancer types by illustrating the possible target genes that are related to each cancer, and we also briefly describe the clinical applications of miR-144s as a diagnostic and prognostic tool in cancers.Int. J. Mol. Sci. 2020, 21, 2578 2 of 23 of a mRNA molecule [3]. MiRNAs indicate a new perspective in the study of cancers. More than 50% of miRNA genes were discovered to be located within the genomic regions that are involved in cancers, suggesting their role in human cancer pathogenesis. In pathological conditions, MiRNAs can negatively regulate gene expression and they are associated with tumor growth, apoptosis, invasion, and metastasis. In the past, several studies have indicated the ability of miRNAs in the inhibition of tumors as a critical option for the improvement of cancer therapy [4,5]. Tumor activator miRNAs, called oncomiRs, are overexpressed in various cancers. On the contrary, suppressive tumor miRNAs are underexpressed [6][7][8]. Among several miRNAs assessed, miR-144s seem to have a role in several cancers. These miRNAs are located in the chromosomal region 17q11.2, being significantly destroyed in many types of cancers. The predicted stem-loop structure of miR-144s recognized by the miRBase (http://mirbase.org/) is shown in Figure 1A. The miR-144 hairpin gives rise to the "guide strand" miR-144-5p and the sister "passenger" strand miR-144-3p ( Figure 1B).

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Section: Mir-144 In Chronic Myeloid Leukemiamentioning

confidence: 99%

MiR-144: A New Possible Therapeutic Target and Diagnostic/Prognostic Tool in Cancers

Kooshkaki

Rezaei

Rahmati

et al. 2020

IJMS

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“…This translocation results in the fusion of the breakpoint cluster region (BCR) gene on chromosome 22 and the Abelson murine leukemia (ABL1) gene on chromosome 9. The product of the BCR-ABL fusion gene, the p210 fusion protein with deregulated tyrosine kinase activity, plays a central role in the pathogenesis of CML [1,2]. CML represents 14 % of all leukemias and 20 % of adult [3].…”

Section: Introductionmentioning

confidence: 99%

“…Ten years ago, the median survival of patients was approximately 4 years due to the progression in fatal accelerated or blastic phases [4]. Today, management of CML has dramatically changed with the advent of tyrosine kinase inhibitors (TKIs), and CML has evolved from a fatal illness to a chronic one [2,4]. Major cytogenetic response (MCR) and complete cytogenetic response (CCR) rates at 12 months were 85 and 69 %, respectively, in the IRIS study [5].…”

Section: Introductionmentioning

confidence: 99%

Pattern of chronic myeloid leukemia in the imatinib era in a Sub-Saharan African setting

et al. 2016

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Chronic myeloid leukemia (CML) is an orphan disease in Africa because of the inaccessibility to specific treatment and the high cost of diagnosis and monitoring patients. The aim of this study was to report CML treatment response in a developing country in the tyrosine kinase inhibitor era. We conducted a longitudinal study of our cohort of CML patients. Socio-demographic, diagnosis, therapeutic, and treatment response parameters were studied. Sokal score, disease phase at diagnosis, delay from diagnosis to treatment, and treatment response were analyzed for their impact on survival. Fifty-five patients with a diagnosis of CML and who received treatment with imatinib for a minimum of 3 months were included in this study. Median follow-up was 170 patient-years. The sex ratio (M/F) was 1.62 and median age at diagnosis was 42 years. At diagnosis, 85.5 % of the patients were in chronic phase (CP), 12.7 % in accelerated phase (AP), and 1.8 % in blast crisis (BC). Sokal risk score distribution was as follows: low risk 29.8 %, intermediate risk 38.3 %, and high risk 31.9 %. Median time from first symptoms to first medical visit was 6.2 months and median time from first medical visit to cytogenetic and or molecular confirmation was 12.4 months. Mean delay time from first medical visit to imatinib initiation was 12.5 months (95 % CI 6.3-18.7). The complete hematologic response (CHR) at 3 months, the major cytogenetic response (MCR) at 12 months, and the major molecular response (MMR) at 24 months were respectively 82.4, 75, and 25 %. The 2-year overall survival rate was 81 %. Advanced phase at the diagnosis, discontinuation of imatinib therapy over 15 % of the time, lack of CHR at 3 months, lack of MCR at 12 months, and progression of the disease during imatinib therapy were associated with a risk of death (p ≤ 0.05). Our data confirm the improved prognosis of CML treated with imatinib in the setting of a developing country. However, response rates are lower than in developed countries, and additional efforts should be made to facilitate early diagnosis and improve access to TKI, treatment compliance, and regular molecular monitoring of patients.

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“…Chronic myelogenous leukemia (CML) is a clonal myeloproliferative and lethal malignancy disorder associated with a specific chromosomal abnormality due to genetic translocation between two different genes on chromosomes 9 and 22 that leads to the expression of the BCR–ABL1 oncoprotein. BCR–ABL1 is an active tyrosine kinase (TK) and can stimulate and activate some downstream pathways that influence the growth, replication, and survival of haematopoietic cells . This type of cancer involves the bone marrow, particularly blood‐forming cells.…”

Section: Introductionmentioning

confidence: 99%

DNA‐binding activity and cytotoxic and cell‐cycle arrest properties of some new coumarin derivatives: a multispectral and computational investigation

et al. 2019

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Coumarins are the most important class of natural compounds found widely in various plants. Many coumarin derivatives with different biological and pharmacological activities have been synthesized. In this study, the antiapoptotic and cytotoxic effects and DNA-binding properties of some synthetic coumarin derivatives (4b, 4d, 4f, 4 g (DBP-g), 4 h and 4j) against K562 cell lines were investigated using different techniques. MTT assay indicated that the DBP-g compound was more active than other derivatives, with a IC 50 value of 55 μM, and therefore this compound was chosen for further investigation. Apoptosis induction was assessed using acridine orange/ethidium bromide double-staining and cell-cycle analysis. In addition, in vitro DNA-binding studies were carried out using ultraviolet-visible light absorption and fluorescence spectroscopy, as well as viscosity measurement and molecular modelling studies. In vitro results indicated that DBP-g interacted with DNA through a groovebinding mode with a binding constant (K b ) of 1.17 × 10 4 M −1 . In agreement with other experimental data, molecular docking studies showed that DBP-g is a minor groove binder. Overall, it can be concluded that DBP-g could be used as an effective and novel chemotherapeutic agent.

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An Overview and Update of Chronic Myeloid Leukemia for Primary Care Physicians

Cited by 67 publications

References 38 publications

MiR-144: A New Possible Therapeutic Target and Diagnostic/Prognostic Tool in Cancers

MiR-144: A New Possible Therapeutic Target and Diagnostic/Prognostic Tool in Cancers

Pattern of chronic myeloid leukemia in the imatinib era in a Sub-Saharan African setting

DNA‐binding activity and cytotoxic and cell‐cycle arrest properties of some new coumarin derivatives: a multispectral and computational investigation

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