Iranian Journal of Pediatric Hematology and Oncology
Volume:9 Issue: 4, Autumn 2019

Malignant disorder with B or T stem cell basis leads to development and continuation of acute lymphoblastic leukemia (ALL) due to aggregation of blast cells in bone marrow. The environmental, genetic, and demographic factors may influence the disease relapse. The objective of this study was to assess the relation between end of induction minimal residual disease and different risk factors in patients with ALL.

This analytic-descriptive study consisted of 91 patients with ALL who referred to Seyed Alshohada Hospital, Isfahan, Iran. The mean age of the patients was 4.91 3.07 years old. The patients were assessed in terms of demographic characteristics, socioeconomic status, and treatment protocol. Their treatment began with Prednisolon, Dexamethason, Vincristine, L-Asparginase (L.APS) or (PEG-ASP), and Anthracycline for 28 days. Then, the end of induction minimal residual disease was assessed in each patient. For data analysis, Spierman, Mann Whitney, and Kruskal wallis tests were applied.

The monthly income level of the patients' families were poor, and we found a significant correlation between monthly income level of the patients' families and the incidence of minimal residual disease (P=0.03). None of the studied factors, including age, the mean of white blood cell count in the first complete blood count, hemoglobin level, platelet level, gender, central nervous system, mediastinal mass, splenomegaly, hepatomegaly, translocation, parents' education, and parents' occupation and response to corticosteroid treatment that might have had not any impacts on the studied disease(p>0.05).

In this study, it was found that assessing the effect of risk factors on the minimal residual disease in patients with leukemia could be a good solution for detecting and eliminating risk factors and increasing the relapse time.

Mammalian cell division is regulated by a complex includes cyclin-dependent kinases (Cdks) and cyclins, Cdk/cyclin complex. The activity of the complex is regulated by Cdk inhibitors (CKIs) compressing CDK4 (INK4) and CDK-interacting protein/kinase inhibitory protein (CIP/KIP) family. Hypermethylation of CKIs has been reported in various cancers. DNA methyltransferase inhibitors (DNMTIs), such as decitabine and 5-aza-2′-deoxycytidine (5-aza-CdR) can reactivate hypermethylated genes. The current study aimed to evaluate the effect of 5-aza-CdR on the expression of p16INK4a, p14ARF, p15INK4b genes, cell viability, and apoptosis in HCC PLC/PRF5 and pancreatic cancer MIA Paca-2 cell lines.

In this laboratory trial, both cell lines were treated with 5-aza-CdR (0, 1, 2.5, 5, 10, 15, and 20 μM) to determine cell viability and then with 3 μM to obtain cell apoptosis and relative gene expression. The cell viability, apoptosis, and genes expression were investigated by 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyl tetrazolium bromide (MTT) assay, flow cytometry, and Real-Time quantitative reverse-transcription polymerase chain reaction (qRT-PCR), respectively.

5-aza-CdR indicated significant inhibitory effect with all used concentrations (P = 0.003). The apoptotic effect of 5-aza-CdR on PLC/PRF5 cells in comparison to pancreatic cancer MIA Paca-2 cells was more significant (P= 0.001). Real-time quantitative PCR analysis revealed that treatment with 5-aza-CdR (3 μM) for 24 and 48h up-regulated p16INK4a, p14ARF, p15INK4b genes expression significantly(P=0.040).

Reactivation of p16INK4a, p14ARF, p15INK4b genes by 5-aza-CdR can induce apoptosis and inhibit cell viability in HCC, PLC/PRF5, and pancreatic cancer, MIA Paca-2, cell lines.

HOX genes are an exceedingly preserved family of homeodomain-involving transcription factors. They are related to a number of malignancies, comprising acute myeloid leukemia (AML). This study aimed to evaluate the effect of HOXB1 7bp deletion mutation on HOXB1gene expression in 36 individuals.

The present cross-sectional study was done on a large Iranian family. In this experimental study, 5 homozygous 7bp deletion individuals along with their unaffected siblings and their parents were investigated. The candidate gene, HOXB1 was screened and analyzed in blood samples of these participants. After RNA extraction, cDNA was synthesized according to manufacturer’s protocol. HOXB1 expression level was analyzed by 2ΔΔCT method. All laboratory procedures used in this experimental study were carried out in genetic laboratory of Shahid Sadoughi University of Medical Sciences.

Sequence analysis of HOXB1 gene by ABI Prism 3130 Genetic Analyzer (Applied Biosystems, Foster City, CA, USA) revealed a family with 5 homozygous (22±17 years) and 22 healthy heterozygous carriers (42±19 years) for 7bp deletion in HOXB1 gene along with 9  healthy wild type (55±41 years). Gene expression analysis by RT-qPCR demonstrated that expression level of HOXB1 gene in wild type and heterozygous carriers specimens had similar levels (p=0.05).

Although HOXB1 mutations has been reported in AML, but association between HOXB1 mutation and AML was not found in our study. Additionally, HOXB1 expression levels showed no significant difference between wild type and heterozygous carriers. So, HOXB1 gene expression cannot provide a powerful tool to differentiate wild type from heterozygous carries.

The origin and function of human leukocyte antigen (HLA) class I molecules on platelets are still highly arguable. Given the differences in the results of the previous studies in this regard, the lack of research in recent years, and the clinical importance of HLA class I molecules, the absorption capacity of platelets for soluble HLA class I molecules was studied in this investigation.

In this experimental study, HLA-A2 antigen was purified from a B cell precursor leukemia cell line (Nalm-6) by cell membrane protein solubilization and usage of HLA-A2 affinity column. Platelet concentrates (PCs) were received from Tehran Blood Transfusion Center. Eighteen bags of HLA-A2-negative PCs were prepared randomly and treated with various concentrations of the purified HLA antigen (100, 500, and 1000 ng/ml) for 48 to 72 hours. Subsequently, the HLA-A2 levels were evaluated on platelets by flow cytometery technique. Data were evaluated using repeated measure ANOVA.P-values less than 0.05 were considered significant.

The results of this study showed that the purified protein was an HLA molecule (HLA-A2).  After the treatment of platelets and HLA molecules, platelets inability was shown for the attracting of HLA molecules. This finding was true in both media of RPMI and plasma. The differences between the case (HLA-treated platelets) and control (untreated platelets) were not significant (p-values> 0.05).

Platelets were unable to significantly adsorb exogenous HLA antigens from their environment. Further studies are needed to unravel the nature and origin of HLA molecules on platelets.

Deferasirox (DFX), Deferoxamine (DFO), and Deferiprone (DFP) are iron chelators that can be used in thalassemic patients with iron overload.

This clinical trial was performed on 108 thalassemic patients who were randomly divided into group A (n=54) and B (n=54). Group A received combination of DFX and DFP, and group B received DFO and DFP for six months. Serum ferritin level was measured at the beginning of the study, 3, and 6 months after the treatment; The heart and liver iron deposition rates were also measured at the beginning of the study, and 6 months after the treatment  in both groups and compared using Magnetic Resonance Imaging T2 plus (MRI T2*).

The mean age of patients in group A and B was 17.29±4.3 and 17.89±5.61 years old, respectively. Serum ferritin level significantly reduced after the treatment (Serum ferritin level at baseline, 3, and 6 months after the treatment in Group A: 2476.25±1289.32, 2089.62±1051.64 and 1290.22±724.78 ng/ml, respectively; in Group B: 2044.63±989.82, 1341.30±887.62 and 1229.41±701.22 ng/ml, respectively) (p<0.01, for both groups). MRI T2* heart and liver was also improved at the end of the study in both groups (p<0.01, for both groups). However, the combination of DFO/DFP significantly decreased severity grades of liver iron deposition in comparison to DFX/DFP regimen after six months (p<0.01).

The results of the present study indicated that both combination therapies of DFO/DFP and DFX/DFP could improve heart and liver MRI T2*. However, DFO/DFP combination therapy was more effective in reducing the severity grades of liver iron deposition.

Cancer is one of the most common diseases in children. Cancer in children can cause many problems for parents, and impose heavy care burden on them, which can lead to negative health consequences. The aim of this study was to determine caregiving burden and relevant influential factors among parents of children with cancer.

This cross-sectional descriptive study was done on 125 parents of children with cancer in oncology department of Shohada Hospital, Tehran, Iran, during March to August 2017. Caregiving burden was measured using the Caregiver Burden Scale. Descriptive statistics, independent-samples T test, one-way ANOVA, Pearson’s correlation analysis, and multivariate linear regression analysis (stepwise method) were used in data analysis with SPSS software (v.19).

The mean score of parents’ care burden was 52.76 ± 10.  Moreover, 17.6%, 71.2% and 11.2% of parents had low, moderate, and high care burden, respectively. Regression analyses indicated that the factors associated with care burden were cancer type (Acute myeloid leukemia (β=0.36, p<0.001) and Ewing sarcoma (β=0.16, p=0.007)), the number of hospitalization (β=0.38, p<0.001), duration of disease (β=-0.31, p<0.001), parent’s age (β=-0.29, p<0.001), parent’s income (β=-0.23, p<0.001), and child’s age (β=0.24, p<0.001). These variables accounted for 65% of the variance in care burden.

The result of this study demonstrated that most of parents of children with cancer had moderate levels of care burden. Different variables increased care burden in parents. Therefore, planning for holistic interventions to reduce care burden in parents and improve quality of care is necessary.

Advances in the management of transfusion dependent thalassemic patients have improved the survival of these patients. The most important consequence of repeated and frequent transfusions is iron accumulation in vital organs. The magnetic resonance imaging (MRI) is a non-invasive and valid technique for the estimation of iron stores. Despite multiple studies about cardiac and liver MRI T2*, there is limited experience about pancreatic MRI. Although there is a weak correlation between hepatic and pancreatic siderosis, MRI assessment of iron deposition in the pancreas can reduce cardiac morbidity. Pancreatic siderosis may be a predictor for the development of glucose dysregulation. Pancreatic R2* > 100 Hz is a risk factor for glucose intolerance or even overt diabetes. Splenectomy can accentuate the pancreatic iron overload. Early intensive chelation therapy in thalassemia patients can reverse glucose metabolism impairment. In this review, the MRI assessment of pancreatic iron overload in transfusion dependent thalassemia, the correlation between pancreas with liver and myocardial hemosiderosis and the importance of pancreatic iron overload in pathogenesis of diabetes mellitus in these patients were discussed.

Biologically, Acute myeloid leukemia (AML) is highly heterogenous. AML with cup-like blast morphology variant has been reported to have important role in risk group stratification and treatment implications. In pediatric age group, this morphology and its clinical implication is rarely discussed. Although this morphology variant is not stated in World Health Organization (WHO) classification of Tumours of Haematopoietic and Lymphoid Tissues, it is associated with poor outcome from the association with other features. A 10- year old girl diagnosed to have AML with this morphology variant is reported in this study. Her laboratory features were hyperleucocytosis, high D-dimer, and blasts morphology of cup-like cells and few mimic the bilobed features of acute promyelocytic leukemia (APML). Further investigation showed clinical and laboratory features similar to what had been reported before in adults, including the presence of adverse marker of Fms-like tyrosine kinase 3 (FLT3) mutation. She was treated with chemotherapy, following which the bone marrow examination documented marrow in remission. Unfortunately, she succumbed to the disease complication from sepsis and marrow failure after few months of diagnosis. Haemato-morphologists might consider this unique morphological recognition and correlate it with other findings, including molecular testing for proper clinical evaluation. The blast feature and haematological findings could predict the clinical behaviour of this type of AML and guide the patient management. This morphological variant serves an important role especially if molecular testing is not available in some parts of the world or at the time of presentation when the result is still pending.