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Aberrant DNA Methylation of SOCS1 Gene is Not Associated with Resistance to Imatinib Mesylate among Chronic Myeloid Leukemia Patients

Elias MH, Azlan H, Baba AA, Ankathil R

Cardiovasc Hematol Disord Drug Targets, 2018;18(3):234-238.
PMID: 29669505 DOI: 10.2174/1871529X18666180419101416

BACKGROUND: In exploring the cause of Imatinib Mesylate (IM) resistance among Chronic Myeloid Leukemia (CML) patients who do not harbor BCR-ABL dependent mechanism, BCR-ABL independent pathways are the most probable pathways that should be explored. In BCR-ABL independent pathway, SOCS1 plays an important role as it helps in regulating optimal JAK/STAT activity.
OBJECTIVE: To identify the association of SOCS1 gene hypermethylation in mediating IM Resistance.
METHOD: The SOCS1 promoter methylation level of 92 BCR-ABL non mutated IM resistant CML patients, 83 IM good response CML patients and 5 normal samples from healthy individuals were measured using Methylation Specific-High Resolution Melt (MS-HRM) analysis.
RESULTS: Both primers used to amplify promoter region from -333 to -223 and from -332 to -188 showed less than 10% methylation in all CML and normal samples. Consequently, there was no significant difference in SOCS1 promoter methylation level between IM resistant and IM good response patients.
CONCLUSION: SOCS1 promoter methylation level is not suitable to be used as one of the biomarkers for predicting the possibility of acquiring resistance among CML patients treated with IM.

Matched MeSH terms: Leukemia, Myeloid/drug therapy*
Fulltext Chronic myeloid leukaemia in Malaysian children

Sinniah D, Ariffin WA, Shiong HW, Lin HP

Singapore Med J, 1981 Dec;22(6):350-3.
PMID: 6950522

A 13 year review at the University Hospital, Kuala Lumpur reveals that chronic myeloid leukaemia (CML) constitutes 4.3% of all childhood leukaemia. Adult type of CML occurs in older children and is associated with marked splenomegaly, leukocytosis and thrombocytosis and the presence of Philadelphia chromosome. Although the initial response to busulphan was encouraging most of the patients succumbed; 2 patients underwent acute lymphoblastic transformation. Juvenile CML occurs in younger children and is associated with less marked splenomegaly, leukocytosis and thrombocytopenia and the presence of elevated fetal haemoglobin levels. The disease is characterised by an acute fulminating course. Despite improved survival in acute lymphoblastic leukaemia, the outlook for chronic myeloid leukaemia in childhood remains poor and treatment needs re-evaluation.

Matched MeSH terms: Leukemia, Myeloid/drug therapy
Neutropenic enterocolitis treated by primary resection with anastomosis in a leukaemic patient receiving chemotherapy

Anderson PE

Aust N Z J Surg, 1993 Jan;63(1):74-6.
PMID: 8466468

Neutropenic enterocolitis is a complication of patients receiving chemotherapy for malignant disease. It has a characteristic presentation and may lead to gut perforation with consequent high mortality. It is best treated by early surgical intervention. Considerable mortality is inevitable in these gravely ill patients.

Matched MeSH terms: Leukemia, Myeloid/drug therapy
Treating childhood acute myeloid leukaemia with the AML-BFM-83 protocol: experience in a developing country

Chan LL, Abdel-Latif ME, Ariffin WA, Ariffin H, Lin HP

Br J Haematol, 2004 Sep;126(6):799-805.
PMID: 15352983

Treatment for childhood acute myeloid leukaemia (AML) consists of remission induction chemotherapy followed by postremission chemotherapy with or without bone marrow transplantation. The AML Berlin-Frankfurt-Munster (BFM)-83 protocol with induction-consolidation-maintenance chemotherapy for 2 years has been reported to result in a 6-year event-free survival (EFS) and event-free interval (EFI) of 49% and 61% respectively. A total of 174 Malaysian children were treated with this protocol between 1985 and 1999. The 5-year EFS and EFI was 30.7% and 48.0% respectively. The overall mortality from sepsis was 24%, which needs urgent address. The 5-year EFS for patients treated before 1993 and after 1993 was 18.6% and 41.3%, respectively (P = 0.04), while the EFI was 32% and 60.6% respectively (P = 0.034). The improvement seen after 1993 was related to a reduction in induction deaths for that period and probably reflected increased capability and familiarity to cope with the demands of the AML-BFM-83 protocol and accompanying complications in the treatment of AML.

Matched MeSH terms: Leukemia, Myeloid/drug therapy*
Retinopathy in acute leukaemia at initial diagnosis: correlation of fundus lesions and haematological parameters

Reddy SC, Jackson N

Acta Ophthalmol Scand, 2004 Feb;82(1):81-5.
PMID: 14738490

PURPOSE: To determine the prevalence of retinal changes in newly diagnosed acute leukaemia patients, and to establish the relationship between retinal lesions and haematological parameters in these patients.
METHODS: A total of 127 patients with acute leukaemia (myeloid and lymphoid), of both genders, aged between 13 and 77 years, were examined by an ophthalmologist for retinal changes using direct/indirect ophthalmoscopy within 2 days of diagnosis before starting chemotherapy.
RESULTS: Retinal lesions were seen in 62 cases (49%), with intraretinal haemorrhages being the most common lesion (42%). A high white blood cell count was significantly associated with intraretinal haemorrhages (p = 0.04) and white-centred haemorrhages (p = 0.001), while a low platelet count was significantly associated with intraretinal haemorrhages (p = 0.03) in acute myeloid leukaemia patients.
CONCLUSIONS: A high white blood cell count may be considered as important as a low platelet count in the pathogenesis of leukaemic retinopathy.

Matched MeSH terms: Leukemia, Myeloid/drug therapy
Nutritional status and dietary intake of children with acute leukaemia during induction or consolidation chemotherapy

Tan SY, Poh BK, Nadrah MH, Jannah NA, Rahman J, Ismail MN

J Hum Nutr Diet, 2013 Jul;26 Suppl 1:23-33.
PMID: 23701375 DOI: 10.1111/jhn.12074

The assessment of nutritional status among paediatric patients is important for the planning and execution of nutritional strategies that strive to optimise the quality of life and growth among sick children. The present study aimed to evaluate the nutritional status and dietary intake among children with acute leukaemia.

Matched MeSH terms: Leukemia, Myeloid/drug therapy
Expression of multidrug resistance (MDR) proteins and in vitro drug resistance in acute leukemias

Fazlina N, Maha A, Jamal R, Zarina AL, Cheong SK, Hamidah H, et al.

Hematology, 2007 Feb;12(1):33-7.
PMID: 17364990

The expression of the multidrug resistance (MDR) proteins may influence the outcome of treatment in patients with acute leukemia. The aim of this study was to determine the IC50 of cytotoxic drugs (cytosine arabinoside, ara-C and daunorubicin, dnr) using the in vitro 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)2H-tetrazolium, inner salt (MTS) assay method. A total of 82 newly diagnosed acute leukemia cases (43 adult myeloid leukaemia, AML cases and 39 acute lymphoblastic leukaemia, ALL cases) and 16 relapsed cases (8 AML cases and 8 ALL cases) were studied. The MTS assay was performed using two cytotoxic drugs, dnr and ara-C. Cells were incubated with different concentrations of drugs for 4 days and the IC50 was extrapolated from the viability curve. In newly diagnosed cases, we found that childhood ALL samples showed higher IC50 values of dnr (0.040 +/- 2.320) compared to adult AML samples (0.021 +/- 0.158). In contrast, newly diagnosed adult AML samples showed higher IC50 values of ara-C (0.157 +/- 0.529) compared to childhood ALL samples (0.100 +/- 2.350). In relapsed cases, two samples of childhood ALL showed IC50 values of dnr (0.910 +/- 1.760) and ara-C (1.310 +/- 2.390), which was higher compared to childhood AML samples (0.129 +/- 0.214 and 0.210 +/- 0.003, respectively). However, there was no correlation between IC50 values of these drugs tested with clinical outcome. In conclusion, we found that MTS assay is an easy, rapid and non laborious method to study in vitro drug resistance in acute leukaemia cases.

Matched MeSH terms: Leukemia, Myeloid/drug therapy