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نوع الوثيقة : مقال في مجلة دورية 
عنوان الوثيقة :
High frequency and poor prognosis of late childhood BCR-ABL-positive and MLL-AF4-positive ALL define the need for advanced molecular diagnostics and improved therapeutic strategies in pediatric B-ALL in Pakistan
High frequency and poor prognosis of late childhood BCR-ABL-positive and MLL-AF4-positive ALL define the need for advanced molecular diagnostics and improved therapeutic strategies in pediatric B-ALL in Pakistan
 
لغة الوثيقة : الانجليزية 
المستخلص : BACKGROUND: Fusion oncogenes (FOs) resulting from chromosomal abnormalities have an important role in leukemogenesis in pediatric B cell acute lymphoblastic leukemia (ALL). The most common FOs are BCR-ABL, MLL-AF4, ETV6-RUNX1, and TCF3-PBX1, all of which have important prognostic and drug selection implications. Moreover, frequencies of FOs have ethnic variations. We studied Pakistani frequencies of FOs, clinical pattern, and outcome in pediatric B-ALL. METHODS: FOs were studied in 188 patients at diagnosis using reverse transcriptase-polymerase chain reaction (RT-PCR) and interphase fluorescent in situ hybridization (FISH). Data were analyzed using SPSS version 17 (SPSS Inc., Chicago, IL, USA). RESULTS: FOs were detected in 87.2 % of patients. Mean overall survival was 70.9 weeks, 3-year survival was 31.9 %, and 3-year relapse-free survival was 18.1 %. Four patients died of drug toxicities. ETV6-RUNX1 (19.14 %) had better survival (110.9 weeks; p = 0.03); TCF3-PBX1 (2.1 %) was associated with inferior outcome and higher central nervous system (CNS) relapse risk; MLL-AF4 (18.1 %) was more common in the 8- to 15-year age group (24/34; p = 0.001) and was associated with organomegaly, low platelet count, and poor survival; and BCR-ABL (47.9 %) was associated with older age (7-15 years, 52/90), lower remission rates, shorter survival (43.73 ± 4.24 weeks) and higher white blood cell count. Overall, MLL-AF4 and BCR-ABL were detected in 66 % of B-ALL, presented in later childhood, and were associated with poor prognosis and inferior survival. CONCLUSIONS: This study reports the highest ethnic frequency of BCR-ABL FO in pediatric ALL, and is consistent with previous reports from our region. Poor prognosis BCR-ABL and MLL-AF4 was detected in two-thirds of pediatric B-ALL and is likely to be the reason for the already reported poor survival of childhood ALL in South-East Asia. Furthermore, MLL-AF4, usually most common in infants, presented in later childhood in most of the ALL patients, which was one of the unique findings in our study. The results presented here highlight the need for mandatory inclusion of molecular testing for pediatric ALL patients in clinical decision making, together with the incorporation of tyrosine kinase inhibitors, as well as hematopoietic stem cell transplantation facilities, to improve treatment outcome for patients in developing countries. 
ردمد : 1177-1062 
اسم الدورية : Molecular diagnosis & therapy 
المجلد : 19 
العدد : 5 
سنة النشر : 1436 هـ
2015 م 
نوع المقالة : مقالة علمية 
تاريخ الاضافة على الموقع : Thursday, April 21, 2016 

الباحثون

اسم الباحث (عربي)اسم الباحث (انجليزي)نوع الباحثالمرتبة العلميةالبريد الالكتروني
Zafar IqbalIqbal, Zafar باحث رئيسي drzafar.medgen@yahoo.com
Tanveer AkhtarAkhtar, Tanveer باحث مشارك  
Tashfin AwanAwan, Tashfin باحث مشارك  
Aamer AleemAleem, Aamer باحث مشارك  
Noreen SabirSabir, Noreen باحث مشارك  
Mahmood RasoolRasool, Mahmood باحث مشارك  
Muhammad AbsarAbsar, Muhammad باحث مشارك  
Afia M AkramAkram, Afia Mباحث  
Masood A ShammasShammas, Masood Aباحث مشارك  
Ijaz H ShahShah, Ijaz Hباحث مشارك  
M KhalidKhalid, M باحث مشارك  
A S TajTaj, A Sباحث مشارك  
A JameelJameel, A باحث مشارك  
A AlanaziAlanazi, A باحث مشارك  
A T GillGill, A Tباحث مشارك  
J A HashmiHashmi, J Aباحث مشارك  
A HussainHussain, A باحث مشارك  
M F SabarSabar, M Fباحث مشارك  
A M KhalidKhalid, A Mباحث مشارك  
M H QaziQazi, M Hباحث مشارك  
S KarimKarim, S باحث مشارك  
M H SiddiqiSiddiqi, M Hباحث مشارك  
A MahmoodMahmood, A باحث مشارك  
M IqbalIqbal, M باحث مشارك  
A SaeedSaeed, A باحث مشارك  
M I IrfanIrfan, M Iباحث مشارك  

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