Emine Türkkan

Deregulated WNT signaling in childhood T-cell acute lymphoblastic leukemia

WNT signaling has been implicated in the regulation of hematopoietic stem cells and plays an important role during T-cell development in thymus. Here we investigated WNT pathway activation in childhood T-cell acute lymphoblastic leukemia (T-ALL) patients. To evaluate the potential role of WNT signaling in T-cell leukomogenesis, we performed expression analysis of key components of WNT pathway. More than 85% of the childhood T-ALL patients showed upregulated β-catenin expression at the protein level compared with normal human thymocytes. The impact of this upregulation was reflected in high expression of known target genes (AXIN2, c-MYC, TCF1 and LEF). Especially AXIN2, the universal target gene of WNT pathway, was upregulated at both mRNA and protein levels in ∼40% of the patients. When β-CATENIN gene was silenced by small interfering RNA, the cancer cells showed higher rates of apoptosis. These results demonstrate that abnormal WNT signaling activation occurs in a significant fraction of human T-ALL cases independent of known T-ALL risk factors. We conclude that deregulated WNT signaling is a novel oncogenic event in childhood T-ALL.

The Efficacy of Magnetic Resonance Imaging and X-Ray in the Evaluation of Response to Radiosynovectomy in Patients with Hemophilic Arthropathy

Objective: We aimed to assess the role of Magnetic Resonance Imaging (MRI) and X-Ray in the evaluation of response to radiosynovectomy (RS) in patients with hemophilic arthropathy. Material and Methods: Eleven patients who suffered from hemophilic arthropathy with a mean age of 11.7 (range between 7-15) were included in this study. 148-185 MBq Yttrium 90 silicate (Y-90) was administered intraarticularly to ten knee joints and one patient was treated with intraarticular 74 MBq Rhenium 186 (Re-186) injection into his ankle. Before radiosynovectomy, plain anteroposterior and lateral X-rays of the target joints were obtained by standard technique. The follow-up MRI and X-ray studies of the patients were done 6 months after RS. Pettersson hemophilic arthropathy scales were utilized to stage the condition of the joints on plain X-ray and classification of the investigated joints on MRI were done according to Denver score. The clinical assessment of the efficacy of the RS was made with the comparison of the average bleedings before and after the intervention. Results: During the 6-month follow-up period after RS, an improvement in number of hemarthrosis 75% or greater compared with the prior six months occurred in six joints (54.5%). The Pettersson scores worsened in 1/11 (9%), remained unchanged in 9/11 (81.8%), and improved in 1/11 (9%) joints. At the 6-month follow-up, the MRI score worsened in one (9%) and was unchanged in 10/11 joints (90.9%). Conclusion: MRI is a more sensitive tool than plain radiography for evaluating and follow-up of joint disease in persons with hemophilia, but both methods don’t show correlation with the therapeutic response Conflict of interest:None declared.

Evaluation of PAX5 gene in the early stages of leukemic B cells in the childhood B cell acute lymphoblastic leukemia.

B-lineage acute lymphoblastic leukemia (B-ALL) is a common subtype of acute leukemia in children. PAX5 plays a central role in B-cell development and differentiation. In this study, we analyzed PAX5 expression levels, transactivation domain mutations/deletions in B-ALL patients (n=115) and healthy controls (n=10). Relative PAX5 mRNA levels were significantly increased in B-ALL patients (p<0.0001). PAX5 expression was also evaluated in three different B-ALL subgroups (pro B, Common B and Pre B ALL) and showed stage specific expression levels. Pro B (p=0.04) and pre B (p=0.04) patients showed significantly high PAX5 mRNA levels compared to stage specific controls. At least one deletion of exons 7-8 or 9 has been identified in the 41% of the patients. CD34 positivity in patients and presence of large deletions (Δ7/8/9) showed a significant correlation (p=0.05). None of our patients showed PAX5 point mutations, but two previously identified SNPs (rs3780135 and rs35469494) were detected. Our results support that PAX5 is a critical factor in B-ALL development and aberrant PAX5 expression especially at early stages may leads to leukemic transformation.

Levels of Beta-2 Microglobulin and Cystatin C in Beta Thalassemia Major Patients

Aim: Thalassemia is accepted to be the most common genetic disease in the world. This study was performed to establish whether there was a glomerular renal damage, which was usually a less mentioned subject in patients with Beta Thalassemia Major, and to compare urea, creatinine and creatinine clearance with early indicators of kidney damage as Cystatin-C and β-2 microglobulin as on determining the glomerular damage. Material and Method: This study was prospectively performed in patients, who were regularly followed in the children hematology outpatient clinic with a diagnosis of Beta Thalassemia Major. Results: There was no statistically significant difference between urea and levels of creatinine clearance and Cystatin-C. There was a statistically negative relationship between creatinine and creatinine clearance at an advanced level as 53.7% (p: 0.002, p<0.01). There was not any significant relationship between Cystatin-C and levels of creatinine and B-2 microglobulin. There was a significant high positive relationship between Cystatin-C and B-2 microglobulin at level of 86.1% (p: 0.001; p<0.01). Discussion: The results of our study were also similar to the literature. However, new studies are required to carry out in wider populations in order to reach definite conclusions about correlation of renal parameters with each other.

Deferasirox in children with transfusion-dependent thalassemia or sickle cell anemia: a large cohort real-life experience from Turkey (REACH-THEM)

To evaluate the long‐term efficacy and safety of deferasirox therapy in a large observational cohort of children with transfusion‐dependent thalassemia (TDT) and sickle cell anemia (SCA) in Turkey.

Aleukemic Leukemia Cutis: An Unusual Rash in a Child

Figure 1.Erythematous macules on the abdomen.

The effects of iron deficiency anemia on thyroid hormones

The Effects Of Iron Deficiency Anemia On Thyroid Hormones Fatma Demir, Ufuk Yükselmiş, Mehmet Yusuf Sarı, Gökten Korkmaz, Emine Türkkan, Servet Erdal Adal Dokuz Eylül Üniversitesi Tıp Fakültesi, Çocuk Hematoloji-onkoloji Bilim Dalı, İzmir Çukurova Üniversitesi Tıp Fakültesi, Çocuk Yoğun Bakım Bilim Dalı, Adana Okmeydanı Eğitim Ve Araştırma Hastanesi, Çocuk Sağlığı Ve Hastalıkları Kliniği, İstanbul