Patients' perceptions about diagnosis and treatment of chronic myeloid leukemia: a cross-sectional study among Brazilian patients

Hamerschlak, Nelson; Souza, Cármino Antônio de; Cornacchioni, Ana Lucia; Pasqüini, Ricardo; Tabak, Daniel; Spector, Nelson; Steagall, Merula

doi:10.1590/1516-3180.2014.0001306

Cited by 4 publications

(4 citation statements)

References 38 publications

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“…4,5 The mechanisms favoring the growth advantage of Philadelphia chromosome-positive cells over normal cells in CML are not fully elucidated but could be partly because of altered apoptosis and longer survival of CML clones. 6,7 Also, little is known about the biologic characteristics of disease progression in CML.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Functional studies of miR-130a on the inhibitory pathways of apoptosis in patients with chronic myeloid leukemia

et al. 2015

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The p53 mutation in chronic myeloid leukemia (CML) led to decreased overall survival and therapy resistance which was also closely correlated with the downstream proto-oncogenes BCL-2, TCL-1 and MCL-1. We in this study aimed to investigate the function of miR130a in p53 tumor suppressor signaling pathway. We performed microRNA (miRNA) expression profile analysis in CML cancer stem cells of 38 cases and extracted total RNA from peripheral blood of 143 cases. Standard curves of U6 and miRNA were made from 10-fold serial dilutions of the cDNA, which were quantified using real-time quantitative PCR with SYBR Green by ABI 7300. The p53 mutations and BCR/ABL mutation status analysis in CML patients were detected by PCR and direct sequencing. Candidate targets of miR130a of putative relevance in CML pathogenesis were analyzed by bioinformatics approach. We then used dual-luciferase activity assay to verify the target genes of miR130a and used western blot analysis to elucidate the mechanism of miR130a on modulating drug resistance. The levels of miR-130a expression in CML were significantly lower in poor prognostic subgroups, defined by prognostic factors including mutated BCR/ABL status, p53 and ATM deletions and p53 mutations. Furthermore, underexpression of miR-130a was significantly associated with shorter overall survival and treatment-free survival in CML patients. We demonstrated that miR130a function as tumor suppressors by inhibiting multiple anti-apoptosis proteins, including BCL-2, MCL-1 and XIAP. This was a direct effect because miR130a negatively regulated expression of a BCL-2/MCL-1/XIAP 3'untranslated region-based reporter construct. Transfection of miR130a mimics into CML cells from 30 patients without p53 aberrations led to significant increases in apoptosis compared with transfection with the miRNA control. Besides, enforced expression of miR130a had no significant drug-sensitization effect in CML cells from p53-attenuated patients. MiR-130a may have an important role in the pathogenesis of CML and may be useful for assessing prognosis in patients with CML. Moreover, miR130a may provide a possible therapeutic avenue and a sensitive indicator of the activity of the p53 in CML.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Functional studies of miR-130a on the inhibitory pathways of apoptosis in patients with chronic myeloid leukemia

et al. 2015

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“…We speculate that this important discontinuation may be related to the patients’ lack of knowledge on the necessity for rigid control of the disease. In fact, a Brazilian study conducted by Hamerschlack et al, 17 in a sample from 8 Brazilian capital cities, concluded that despite patients being diagnosed rapidly and having good access to the treatment, they are lacking in comprehension of the importance of the control measures for CML.…”

Section: Discussionmentioning

confidence: 99%

“…Parasitism was initially supposed to be an important factor interfering in the treatment adherence, taking into consideration the region's undeveloped reality and high parasitism rate. It was believed that clinical signs of certain diseases could be confused, especially by the patient, with imatinib's side effects, such as nausea and vomiting,17, 18, 19 and in that manner lead to intentional discontinuation by the patient. Despite not being significant, it is important to highlight the retrospective nature of this study, which does not invalidate the need for a prospective study in high parasitism rate areas.…”

Section: Discussionmentioning

confidence: 99%

Analysis of imatinib adherence in chronic myeloid leukemia: a retrospective study in a referral hospital in the Brazilian Amazon

Andrade

Leitão

Paz

et al. 2019

Hematology, Transfusion and Cell Therapy

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Background There has been a revolution in the treatment of Chronic Myeloid Leukemia since imatinib's introduction. However, patient adherence has a great impact on the response obtained with medical treatment. This study's objective was to analyze the drug adherence and the factors that influenced it in patients with Chronic Myeloid Leukemia in a referral hospital in the Brazilian Amazon. Method This was a retrospective study including 120 patients with Chronic Myeloid Leukemia from January 2002 to December 2014. The adherence was estimated by the Proportion of Days Covered and the persistence by Kaplan–Meier analysis. The data was analyzed in Epi Info 7 ® software and the relationship between the variables was analyzed by Fisher's exact test. A p -value lower than 0.05 was considered significant. Results Twenty-seven patients (22.5%) were considered non-adherent. There has been irregular medication use and disinterest in the treatment in 20.83% ( n = 25), of which 13 were considered non-adherent ( p < 0.001). A total of 26.67% ( n = 32) abandoned the treatment for a period. Of those, 56.25% ( n = 18) were non-adherent ( p < 0.001). Distance to the hospital, lack of medication and side-effects were all non-significant to low adherence. At the end of a 360-day follow-up, 44.16% ( n = 53) of patients presented a break in persistence, whose average was 255 days. Conclusion The adherence found in this study was similar to that found in others of its kind. The only factors that negatively influenced the adherence were disinterest and abandonment of treatment, which can reflect the need to individually educate Chronic Myeloid Leukemia patients.

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“…O ponatinibe é uma opção após tentativa com os outros inibidores, ou se as células leucêmicas desenvolverem a mutação T315I. Também são utilizados hidroxiureia, interferon-α e transplante de células-tronco hematopoiéticas para tratamento a depender do contexto clínico (HAMERSCHLAK et al, 2015).…”

Section: 4) Tratamento Da Lmc Utilizando Bcr-abl1 Como Alvounclassified

Análises proteômicas aplicadas à Investigação dos mecanismos de resistência celular em leucemia mieloide crônica

Silvestrini

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Investigation of cellular resistance mechanisms in Chronic Myeloid Leukemia using proteomics strategiesPhD thesis -Ribeirão Preto Medical School, University of São Paulo. 2023.Chronic myeloid leukemia (CML) is characterized by the presence of the BCR-ABL1 oncoprotein, with constitutive activation of its tyrosine kinase activity, and the neoplastic transformation of hematopoietic stem cells. The development of BCR-ABL1-specific tyrosine kinase inhibitors (TKIs), such as imatinib mesylate, represented an important advancement in the treatment of CML. However, the current therapeutic challenges are: i-offering patients a long-term cure, without ongoing maintenance of treatment, and, iireducing the impact of resistance to treatment observed in up to 20% of patients. The T315I mutation in BCR-ABL1 produces resistance to all available TKIs. From these demands, the logical rationale for therapeutic complementation based on molecular targets supporting the transforming action of BCR-ABL1 emerges. The identification of the association of the IRS1 adapter protein with BCR-ABL1 and the demonstration of the antineoplastic effects of the pharmacological inhibitor NT157 of IGF1R-IRS1/2 in BCR-ABL1 cell models, regardless of the mutational status for T315I, opened new perspectives for reducing the impact of resistance in patients. Thus, we sought to identify new molecular mechanisms of NT157 and imatinib in BCR-ABL1 cells, mutated or not for T315I, through proteomic analysis. For this, we used in vitro models of murine cell lines Ba/F3 BCR-ABL1 (WT e T315I) that were submitted to treatment with NT157 and/or imatinib and also primary cells from patients with mutation T315I. In order to elucidate the early molecular processes triggered by NT157, we used conditions that do not interfere with cell viability, but that alter survival mechanisms. Detailed proteomic analysis in Ba/F3 cells demonstrated proteins that are NT157 and imatinib-dependent, highlighting regulated processes such as the ubiquitin proteasome system, cellular metabolism and regulation of gene transcription. In primary cells, our results indicated that treatment with NT157 (6.4 µM) decreased viability and increased apoptosis in PBMCs carrying the T315I mutation. Also, through a quantitative proteomic analysis, proteins in the patient's cells stand out, such as the CD70 cytokine, which had its levels increased with NT157 treatment. Changes were also identified in other proteins known to be involved in CML, such as CD44, CD14 and CD33. Our findings suggest that inhibition of IGF1R/IRS signaling has important specificity and opens up the prospect of possible combination therapies with TKI for resistant patients.

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Patients' perceptions about diagnosis and treatment of chronic myeloid leukemia: a cross-sectional study among Brazilian patients

Cited by 4 publications

References 38 publications

RETRACTED ARTICLE: Functional studies of miR-130a on the inhibitory pathways of apoptosis in patients with chronic myeloid leukemia

RETRACTED ARTICLE: Functional studies of miR-130a on the inhibitory pathways of apoptosis in patients with chronic myeloid leukemia

Analysis of imatinib adherence in chronic myeloid leukemia: a retrospective study in a referral hospital in the Brazilian Amazon

Análises proteômicas aplicadas à Investigação dos mecanismos de resistência celular em leucemia mieloide crônica

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