MyMedR

Displaying publications 1 - 20 of 30 in total

Abstract:

Sort:

MicroRNAs that affect the Fanconi Anemia/BRCA pathway are downregulated in imatinib-resistant chronic myeloid leukemia patients without detectable BCR-ABL kinase domain mutations

Yap E, Norziha ZA, Simbun A, Tumian NR, Cheong SK, Leong CF, et al.

Leuk. Res., 2017 08;59:32-40.
PMID: 28544907 DOI: 10.1016/j.leukres.2017.05.015

Chronic myeloid leukemia (CML) patients who do not achieve landmark responses following treatment with imatinib mesylate (IM) are considered IM-resistant. Although IM-resistance can be due to BCR-ABL kinase domain (KD) mutations, many IM-resistant patients do not have detectable BCR-ABL KD mutations. MicroRNAs (miRNAs) are short non-coding RNAs that control gene expression. To investigate the role of miRNAs in IM-resistance, we recruited 8 chronic phase CML patients with IM-resistance who tested negative for BCR-ABL KD mutations and 2 healthy normal controls. Using miRNA sequencing, we identified 54 differentially expressed miRNAs; 43 of them downregulated. The 3 most differentially downregulated miRNAs were miR-146a-5p, miR-99b-5p and miR-151a-5p. Using real-time quantitative reverse transcriptase-polymerase chain reaction, the expression patterns of the 3 miRNAs were validated on the same cohort of 8 patients in addition to 3 other IM-resistant CML patients. In-silico analysis showed that the predicted gene targets are ATRIP, ATR, WDR48, RAD51C and FANCA genes which are involved in the Fanconi Anemia/BRCA pathway. This pathway regulates DNA damage response (DDR) and influences disease response to chemotherapy. Thus it is conceivable that DDR constitutes a key component in IM-resistance. Further research is needed to elucidate miRNA modulation of the predicted gene targets.

Matched MeSH terms: Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy*
Oral and cutaneous lichenoid reaction with nail changes secondary to imatinib: report of a case and literature review

Wahiduzzaman M, Pubalan M

Dermatol. Online J., 2008;14(12):14.
PMID: 19265627

Imatinib mesylate--Gleevec (US), Glivec (worldwide), STI571--is an oral cancer drug that selectively inhibits several protein tyrosine kinases associated with human malignancy. The drug is used for the treatment of chronic myeloid leukemia, malignant gastrointestinal stromal tumors, and some other conditions. Treatment with imatinib is generally well tolerated but not without the risk of adverse effects. The risk of severe adverse events is low. Cutaneous side effects of this drug are common but muco-cutaneous lichenoid eruption with nail changes is very rare. We report a case of lichenoid eruption during imatinib therapy involving the skin, mucous membranes, and nails that cleared in spite of ongoing imatinib therapy.

Matched MeSH terms: Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy
Efficacy of a medication management service in improving adherence to tyrosine kinase inhibitors and clinical outcomes of patients with chronic myeloid leukaemia: a randomised controlled trial

Tan BK, Chua SS, Chen LC, Chang KM, Balashanker S, Bee PC

Support Care Cancer, 2020 Jul;28(7):3237-3247.
PMID: 31734798 DOI: 10.1007/s00520-019-05133-0

PURPOSE: Suboptimal adherence to tyrosine kinase inhibitors (TKIs) contributes to poor clinical outcomes in chronic myeloid leukemia (CML). This randomised controlled trial (RCT) aimed to evaluate the impact of a medication management service (MMS) on adherence to TKIs and clinical outcomes.
METHODS: A parallel RCT was conducted in two hospitals in Malaysia, where 129 CML patients were randomised to MMS or control (usual care) groups using a stratified 1:1 block randomisation method. The 6-month MMS included three face-to-face medication use reviews, CML and TKI-related education, two follow-up telephone conversations, a printed information booklet and two adherence aids. Medication adherence (primary outcome), molecular responses and health-related quality of life (HRQoL) scores were assessed at baseline, 6th and 12th month. Medication adherence and HRQoL were assessed using medication possession ratio and the European Organisation for Research and Treatment in Cancer questionnaire (EORTC_QLQ30_CML24) respectively.
RESULTS: The MMS group (n = 65) showed significantly higher adherence to TKIs than the control group (n = 64) at 6th month (81.5% vs 56.3%; p = 0.002), but not at 12th month (72.6% vs 60.3%; p = 0.147). In addition, a significantly higher proportion of participants in the MMS group achieved major molecular response at 6th month (58.5% vs 35.9%; p = 0.010), but not at 12th month (66.2% vs 51.6%; p = 0.092). Significant deep molecular response was also obtained at 12th month (24.6% vs 10.9%; p = 0.042). Six out of 20 subscales of EORTC-QLQ30-CML24 were significantly better in the MMS group.
CONCLUSIONS: The MMS improved CML patients' adherence to TKI as well as achieved better clinical outcomes.
TRIAL REGISTRATION: Clinicaltrial.gov (ID: NCT03090477).

Matched MeSH terms: Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy*
Fulltext SLC22A1-ABCB1 haplotype profiles predict imatinib pharmacokinetics in Asian patients with chronic myeloid leukemia

Singh O, Chan JY, Lin K, Heng CC, Chowbay B

PLoS One, 2012;7(12):e51771.
PMID: 23272163 DOI: 10.1371/journal.pone.0051771

This study aimed to explore the influence of SLC22A1, PXR, ABCG2, ABCB1 and CYP3A5 3 genetic polymorphisms on imatinib mesylate (IM) pharmacokinetics in Asian patients with chronic myeloid leukemia (CML).

Matched MeSH terms: Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy
Fulltext Pregnancy in a patient receiving busulphan for chronic myeloid leukaemia

Norhaya MR, Cheong SK, Hamidah NH, Ainoon O

Singapore Med J, 1994 Feb;35(1):102-3.
PMID: 8009265

A 33-year-old Malay lady with chronic myeloid leukaemia (CML) became amenorrhoeic during therapy with busulphan. Pregnancy was diagnosed via a urine pregnancy test and an ultrasound confirmed a viable foetus at 16 weeks. The busulphan was stopped. Her pregnancy was unremarkable and continued till term. She delivered a healthy child.

Matched MeSH terms: Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy*
Identification of copy number alterations by array comparative genomic hybridization in patients with late chronic or accelerated phase chronic myeloid leukemia treated with imatinib mesylate

Nadarajan VS, Phan CL, Ang CH, Liang KL, Gan GG, Bee PC, et al.

Int J Hematol, 2011 Apr;93(4):465-473.
PMID: 21387093 DOI: 10.1007/s12185-011-0796-9

The outcome of treating chronic myeloid leukemia (CML) with imatinib mesylate (IM) is inferior when therapy is commenced in late chronic or accelerated phase as compared to early chronic phase. This may be attributed to additional genomic alterations that accumulate during disease progression. We sought to identify such lesions in patients showing suboptimal response to IM by performing array-CGH analysis on 39 sequential samples from 15 CML patients. Seventy-four cumulative copy number alterations (CNAs) consisting of 35 losses and 39 gains were identified. Alterations flanking the ABL1 and BCR genes on chromosomes 9 and 22, respectively, were the most common identified lesions with 5 patients losing variable portions of 9q34.11 proximal to ABL1. Losses involving 1p36, 5q31, 17q25, Y and gains of 3q21, 8q24, 22q11, Xp11 were among other recurrent lesions identified. Aberrations were also observed in individual patients, involving regions containing known leukemia-associated genes; CDKN2A/2B, IKZF1, RB1, TLX1, AFF4. CML patients in late stages of their disease, harbor pre-existing and evolving sub-microscopic CNAs that may influence disease progression and IM response.

Matched MeSH terms: Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy*
Fulltext A case of chronic myeloid leukaemia in blast transformation with leukemic ascites

Mohd Ridzuan MS, Yap E, Wan Fariza WJ, Fadilah SA, Salwati S

Med J Malaysia, 2016 04;71(2):85-7.
PMID: 27326952 MyJurnal

Chronic Myeloid Leukaemia (CML) is a disease characterised by a distinctive marker that is the Philadelphia Chromosome and an ability to transform into blast phase, which confers a poor prognosis. The median survival was reported to be between three to six months in correlation to blast phase. Extramedullary involvement with CML to sites such as pleural, meningeal and bones have been reported. We report a case of 41-year-old man who was diagnosed with CML in blast phase and presented with ascites. Ultrasound of abdomen showed coarse echotexture of liver suggestive leukaemic infiltration to the liver. The liver profile was severely deranged and associated with coagulopathy. Flow cytometry analysis of the peritoneal fluid revealed presence of myeloblasts consistent with CML in blast crisis with leukaemic ascites. Bone marrow biopsy also confirmed disease transformation. He received standard induction chemotherapy for acute myeloid leukaemia with dose modifications based on liver enzymes performance. Our case highlights an unusual presentation of CML in blast crisis with leukaemic ascites and the challenges in managing cytotoxic treatments due to the liver infiltration.

Matched MeSH terms: Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy
Low level of TERC gene amplification between chronic myeloid leukaemia patients resistant and respond to imatinib mesylate treatment

Mohamad Ashari ZS, Sulong S, Hassan R, Husin A, Sim GA, Abdul Wahid SF

Asian Pac J Cancer Prev, 2014;15(4):1863-9.
PMID: 24641422

The amplification of telomerase component (TERC) gene could play an important role in generation and treatment of haematological malignancies. This present study was aimed to investigate copy number amplification status of TERC gene in chronic myeloid leukaemia (CML) patients who were being treated with imatinib mesylate (IM). Genomic DNA was extracted from peripheral blood of CML-IM Resistant (n=63), CML-IM Respond (n=63) and healthy individuals (n=30). TERC gene copy number predicted (CNP) and copy number calculated (CNC) were determined based on Taqman® Copy Number Assay. Fluorescence in situ hybridization (FISH) analysis was performed to confirm the normal signal pattern in C4 (calibrator) for TERC gene. Nine of CML patients showed TERC gene amplification (CNP=3), others had 2 CNP. A total of 17 CML patients expressed CNC>2.31 and the rest had 2.31>CNC>1.5. TERC gene CNP value in healthy individuals was 2 and their CNC value showed in range 1.59-2.31. The average CNC TERC gene copy number was 2.07, 1.99 and 1.94 in CML- IM Resistant patients, CML-IM Respond and healthy groups, respectively. No significant difference of TERC gene amplification observed between CML-IM Resistant and CML-IM Respond patients. Low levels of TERC gene amplification might not have a huge impact in haematological disorders especially in terms of resistance towards IM treatment.

Matched MeSH terms: Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy
Prevalence of BCR-ABL T315I Mutation in Malaysian Patients with Imatinib-Resistant Chronic Myeloid Leukemia

Mat Yusoff Y, Abu Seman Z, Othman N, Kamaluddin NR, Esa E, Zulkiply NA, et al.

Asian Pac J Cancer Prev, 2018 Dec 25;19(12):3317-3320.
PMID: 30583336

Objective: Chronic Myeloid Leukemia (CML) is caused by a reciprocal translocation between chromosomes 9
and 22, t(9;22) (q34;q11) which encodes for the BCR-ABL fusion protein. Discovery of Imatinib Mesylate (IM) as
first line therapy has brought tremendous improvement in the management of CML. However, emergence of point
mutations within the BCR-ABL gene particularly T315I mutation, affects a common BCR-ABL kinase contact residue
which impairs drug binding thus contribute to treatment resistance. This study aims to investigate the BCR-ABL T315I
mutation in Malaysian patients with CML. Methods: A total of 285 patients diagnosed with CML were included in this
study. Mutation detection was performed using qualitative real-time PCR (qPCR). Results: Fifteen out of 285 samples
(5.26%) were positive for T315I mutations after amplification with real-time PCR assay. From the total number of
positive samples, six patients were in accelerated phase (AP), four in chronic phase (CP) and five in blast crisis (BC).
Conclusion: Mutation testing is recommended for choosing various tyrosine kinase inhibitors (TKIs) to optimize
outcomes for both cases of treatment failure or suboptimal response to imatinib. Therefore, detection of T315I mutation
in CML patients are clinically useful in the selection of appropriate treatment strategies to prevent disease progression.

Matched MeSH terms: Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy*
Association of GSTM1, GSTT1 and GSTP1 Ile105Val polymorphisms with clinical response to imatinib mesylate treatment among Malaysian chronic myeloid leukaemia patients

Makhtar SM, Husin A, Baba AA, Ankathil R

J Genet, 2017 Sep;96(4):633-639.
PMID: 28947711

The detoxifying activity of glutathione S-transferases (GST) enzymes not only protect cells from the adverse effects of xenobiotics, but also alters the effectiveness of drugs in cancer cells, resulting in toxicity or drug resistance. In this study, we aimed to evaluate the association of GSTM1, GSTT1 and GSTP1 Ile105Val polymorphisms with treatment response among Malaysian chronic myeloid leukaemia (CML) patients who everyday undergo 400 mg of imatinib mesylate (IM) therapy. Multiplex polymerase chain reaction (multiplex-PCR) was performed to detect GSTM1 and GSTT1 polymorphisms simultaneously and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was conducted to detect the GSTP1 Ile195Val polymorphism. On evaluating the association of the variant genotype with treatment outcome, heterozygous variant (AG) and homozygous variant (GG) of GSTP1 Ile105Val showed significantly a higher risk for the development of resistance to IM with OR: 1.951 (95% CI: 1.186-3.209, P = 0.009) and OR: 3.540 (95% CI: 1.305-9.606, P = 0.013), respectively. Likewise, GSTT1 null genotype was also associated with a significantly higher risk for the development of resistance to IM with OR = 1.664 (95% CI: 1.011-2.739, P = 0.045). Our results indicate the potential usefulness of GST polymorphism genotyping in predicting the IM treatment response among CML patients.

Matched MeSH terms: Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy*
Fulltext Inhibition of euchromatic histone methyltransferase 1 and 2 sensitizes chronic myeloid leukemia cells to interferon treatment

Loh SW, Ng WL, Yeo KS, Lim YY, Ea CK

PLoS One, 2014;9(7):e103915.
PMID: 25079219 DOI: 10.1371/journal.pone.0103915

H3K9 methylation is one of the essential histone post-translational modifications for heterochromatin formation and transcriptional repression. Recently, several studies have demonstrated that H3K9 methylation negatively regulates the type I interferon response.

Matched MeSH terms: Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy*
Hydroxyurea treatment for chronic myeloid leukaemia during pregnancy

Jackson N, Shukri A, Ali K

Br J Haematol, 1993 Sep;85(1):203-4.
PMID: 8251394

A patient being treated for chronic myeloid leukaemia with hydroxyurea became pregnant. Despite an increase in the dose of hydroxyurea (to 3 g per day) during the pregnancy, her white blood cell count could only be controlled at about 150 x 10(9)/l. A healthy baby girl was born at 37 weeks with normal blood counts and no evidence of congenital abnormality. There are now five reports of the use of hydroxyurea in pregnancy, and where leukapheresis is not available it may be the treatment of choice.

Matched MeSH terms: Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy*
Fulltext Nilotinib dose-optimization in newly diagnosed chronic myeloid leukaemia in chronic phase: final results from ENESTxtnd

Hughes TP, Munhoz E, Aurelio Salvino M, Ong TC, Elhaddad A, Shortt J, et al.

Br J Haematol, 2017 10;179(2):219-228.
PMID: 28699641 DOI: 10.1111/bjh.14829

The Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Extending Molecular Responses (ENESTxtnd) study was conducted to evaluate the kinetics of molecular response to nilotinib in patients with newly diagnosed chronic myeloid leukaemia in chronic phase and the impact of novel dose-optimization strategies on patient outcomes. The ENESTxtnd protocol allowed nilotinib dose escalation (from 300 to 400 mg twice daily) in the case of suboptimal response or treatment failure as well as dose re-escalation for patients with nilotinib dose reductions due to adverse events. Among 421 patients enrolled in ENESTxtnd, 70·8% (95% confidence interval, 66·2-75·1%) achieved major molecular response (BCR-ABL1 ≤ 0·1% on the International Scale) by 12 months (primary endpoint). By 24 months, 81·0% of patients achieved major molecular response, including 63·6% (56 of 88) of those with dose escalations for lack of efficacy and 74·3% (55 of 74) of those with dose reductions due to adverse events (including 43 of 54 patients with successful re-escalation). The safety profile of nilotinib was consistent with prior studies. The most common non-haematological adverse events were headache, rash, and nausea; cardiovascular events were reported in 4·5% of patients (grade 3/4, 3·1%). The study was registered at clinicaltrials.gov (NCT01254188).

Matched MeSH terms: Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy*
Fulltext BCR-ABL positive essential thrombocythaemia: a variant of chronic myelogerous leukaemia or a distinct clinical entity: a special case report

Fadilah SA, Cheong SK

Singapore Med J, 2000 Dec;41(12):595-8.
PMID: 11296785

A 37-year-old Malay man presented initially with the clinical picture of essential thrombocythaemia (ET) without the extreme leukocytosis, marked splenomegaly and low neutrophil alkaline phosphatase characteristic of chronic myelogenous leukaemia (CML). Bone marrow examination showed massive megakaryocytic hyperplasia; cytogenetic studies showed the presence of Philadelphia chromosome. The patient was treated with hydroxyurea that resulted in reduction in the platelet count. Seventeen months later, he presented with fever associated with tender massive splenomegaly. Bone marrow finding was consistent with chronic phase CML. The presence of a rearrangement involving the major breakpoint cluster region (M-bcr) on chromosome 22 was confirmed by reverse transcriptase-polymerase chain reaction. The clinical importance of finding the Philadelphia chromosome in patients who seem to have ET is in assessing prognosis. ET generally follows a chronic, indolent course. However, this patient who had Philadelphia chromosome underwent clinical transition to chronic phase CML17 months and blast crisis 29 months after presentation.

Matched MeSH terms: Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy
BCR-ABL kinase domain mutations, including 2 novel mutations in imatinib resistant Malaysian chronic myeloid leukemia patients-Frequency and clinical outcome

Elias MH, Baba AA, Azlan H, Rosline H, Sim GA, Padmini M, et al.

Leuk. Res., 2014 Apr;38(4):454-9.
PMID: 24456693 DOI: 10.1016/j.leukres.2013.12.025

Discovery of imatinib mesylate (IM) as the targeted BCR-ABL protein tyrosine kinase inhibitor (TKI) has resulted in its use as the frontline therapy for chronic myeloid leukemia (CML) across the world. Although high response rates are observed in CML patients who receive IM treatment, a significant number of patients develop resistance to IM. Resistance to IM in patients has been associated with a heterogeneous array of mechanisms of which point mutations within the ABL tyrosine kinase domain (TKD) are the frequently documented. The types and frequencies of mutations reported in different population studies have shown wide variability. We screened 125 Malaysian CML patients on IM therapy who showed either TKI refractory or resistance to IM to investigate the frequency and pattern of BCR-ABL kinase domain mutations among Malaysian CML patients undergoing IM therapy and to determine the clinical significance. Mutational screening using denaturing high performance liquid chromatography (dHPLC) followed by DNA sequencing was performed on 125 IM resistant Malaysian CML patients. Mutations were detected in 28 patients (22.4%). Fifteen different types of mutations (T315I, E255K, G250E, M351T, F359C, G251E, Y253H, V289F, E355G, N368S, L387M, H369R, A397P, E355A, D276G), including 2 novel mutations were identified, with T315I as the predominant type of mutation. The data generated from clinical and molecular parameters studied were correlated with the survival of CML patients. Patients with Y253H, M351T and E355G TKD mutations showed poorer prognosis compared to those without mutation. Interestingly, when the prognostic impact of the observed mutations was compared inter-individually, E355G and Y253H mutations were associated with more adverse prognosis and shorter survival (P=0.025 and 0.005 respectively) than T315I mutation. Results suggest that apart from those mutations occurring in the three crucial regions (catalytic domain, P-loop and activation-loop), other rare mutations also may have high impact in the development of resistance and adverse prognosis. Presence of mutations in different regions of BCR-ABL TKD leads to different levels of resistance and early detection of emerging mutant clones may help in decision making for alternative treatment. Serial monitoring of BCR-ABL1 transcripts in CML patients allows appropriate selection of CML patients for BCR-ABL1 KD mutation analysis associated with acquired TKI resistance. Identification of these KD mutations is essential in order to direct alternative treatments in such CML patients.

Matched MeSH terms: Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy*
Fulltext HOXA4 gene promoter hypermethylation as an epigenetic mechanism mediating resistance to imatinib mesylate in chronic myeloid leukemia patients

Elias MH, Baba AA, Husin A, Sulong S, Hassan R, Sim GA, et al.

Biomed Res Int, 2013;2013:129715.
PMID: 23484077 DOI: 10.1155/2013/129715

Development of resistance to imatinib mesylate (IM) in chronic myeloid leukemia (CML) patients has emerged as a significant clinical problem. The observation that increased epigenetic silencing of potential tumor suppressor genes correlates with disease progression in some CML patients treated with IM suggests a relationship between epigenetic silencing and resistance development. We hypothesize that promoter hypermethylation of HOXA4 could be an epigenetic mechanism mediating IM resistance in CML patients. Thus a study was undertaken to investigate the promoter hypermethylation status of HOXA4 in CML patients on IM treatment and to determine its role in mediating resistance to IM. Genomic DNA was extracted from peripheral blood samples of 95 CML patients (38 good responders and 57 resistant) and 12 normal controls. All samples were bisulfite treated and analysed by methylation-specific high-resolution melt analysis. Compared to the good responders, the HOXA4 hypermethylation level was significantly higher (P = 0.002) in IM-resistant CML patients. On comparing the risk, HOXA4 hypermethylation was associated with a higher risk for IM resistance (OR 4.658; 95% CI, 1.673-12.971; P = 0.003). Thus, it is reasonable to suggest that promoter hypermethylation of HOXA4 gene could be an epigenetic mechanism mediating IM resistance in CML patients.

Matched MeSH terms: Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy
Fulltext Aberrant DNA methylation at HOXA4 and HOXA5 genes are associated with resistance to imatinib mesylate among chronic myeloid leukemia patients

Elias MH, Azlan H, Sulong S, Baba AA, Ankathil R

Cancer Rep (Hoboken), 2018 08;1(2):e1111.
PMID: 32721103 DOI: 10.1002/cnr2.1111

BACKGROUND: Imatinib mesylate is a molecularly targeted tyrosine kinase inhibitor drug. It is effectively used in the treatment of chronic myeloid leukemia (CML) patients. However, development of resistance to imatinib mesylate as a result of BCR-ABL dependent and BCR-ABL independent mechanisms has emerged as a daunting problem in the management of CML patients. Between these mechanisms, BCR-ABL independent mechanisms are still not robustly understood.
AIM: To investigate the correlation of HOXA4 and HOXA5 promoter DNA hypermethylation with imatinib resistance among CML patients.
METHODS AND RESULTS: Samples from 175 Philadelphia positive CML patients (83 good response and 92 BCR-ABL non-mutated imatinib resistant patients) were subjected to Methylation Specific High Resolution Melt Analysis for methylation levels quantification of the HOXA4 and HOXA5 promoter regions. Receiver operating characteristic curve analysis was done to elucidate the optimal methylation cut-off point followed by multiple logistic regression analysis. Log-Rank analysis was done to measure the overall survival difference between CML groups. The optimal methylation cut-off point was found to be at 62.5% for both HOXA4 and HOXA5. Chronic myeloid leukemia patients with ≥63% HOXA4 and HOXA5 methylation level were shown to have 3.78 and 3.95 times the odds, respectively, to acquire resistance to imatinib. However, overall survival of CML patients that have ≤62% and ≥ 63% methylation levels of HOXA4 and HOXA5 genes were found to be not significant (P-value = 0.126 for HOXA4; P-value = 0.217 for HOXA5).
CONCLUSION: Hypermethylation of the HOXA4 and HOXA5 promoter is correlated with imatinib resistance and with further investigation, it could be a potential epigenetic biomarker in supplement to the BCR-ABL gene mutation in predicting imatinib treatment response among CML patients but could not be considered as a prognostic marker.

Matched MeSH terms: Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy*
Late-onset marrow aplasia due to imatinib in newly diagnosed chronic phase chronic myeloid leukaemia

Chng WJ, Tan LH

Leuk. Res., 2005 Jun;29(6):719-20.
PMID: 15863215
Matched MeSH terms: Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy*
Fulltext Rechallenge of ponatinib in chronic myeloid leukaemia after hepatotoxicity

Boo YL, Liam CCK, Toh SG, Lim SM

Hong Kong Med J, 2019 04;25(2):162-163.
PMID: 30971509 DOI: 10.12809/hkmj187420
Matched MeSH terms: Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy*
Fulltext Cardiovascular event in chronic myeloid leukaemia treated with tyrosine kinase inhibitor: a case report

Boo YL, Liam CCK, Lim SY, Look ML

Hong Kong Med J, 2019 Feb;25(1):74-5.
PMID: 30713145 DOI: 10.12809/hkmj176972
Matched MeSH terms: Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy*

Filters

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links