Krebswissenschaft und -therapie

CD44 and CD44 Variant 6 in Children with Acute Lymphoblastic Leukemia

Abstract

Ahmad A Omran, Esmat A Elsharkawy, Ayman G Ghobrial, Hosny B Hamed, Waleed M Abd el Hameed, Nagwa I Okaily and Abdel-Azeem M. El-Marazy

Background and objectives: Acute lymphoblastic leukemia (ALL) is a malignant disorder of lymphoid progenitor cells. Many prognostic factors are important for therapeutic assignment. The cell adhesion molecule CD44 is involved in pathologic activities of tumour cells and hematological malignancies. CD44v6 is an important isoform of CD44 family. It plays an important role in the growth and metastasis development in some hematological malignancies The aim of this study is to detect CD44 and CD44v6 expression in children with acute lymphoblastic leukemia and to correlate them with prognosis and other standard prognostic factors for ALL.

Subjects and methods: The study carried out on 57 children divided into: group Ӏ included 40 newly diagnosed children with acute lymphoblastic leukemia who were followed up for one year and group II 17 apparently healthy children of matched age and sex (as control group). Each child was subjected to complete history taking, clinical examination, laboratory investigations in the form of routine investigations; CBC, Leishman-stained peripheral blood smears, LDH. Bone marrow aspiration, Myeloperoxidase-stained peripheral blood, bone marrow smears, Immunophenotyping on BM/PB samples determined by Flowcytometer for routine panel of acute leukemia. Special investigations in the form of; flowcytometeric analysis of CD44 and CD44v6 mRNA expression by quantitative RTPCR were done for all children.

Results: CD44 expression was significantly higher in group I than group II (P=0.001) while there was no significant difference between CD44v6 in group I and group II . Significant positive correlation between CD44% and LDH level, total leucocytic count and bone marrow blast cell ( r=0.64, P=0.001 & r=0.62, P=0.001 & r=0.92, P=0.001) respectively, However there was statistically significant negative correlation between CD44% , hemoglobin(HB) level and platelet count (r=-0.93, P=0.001 & r=-0.92, P=0.001) respectively. CD44%, white blood cell count, Percentage of cases with lymphadenopathy and/or splenomegaly was significantly higher in children with unfavorable outcome. There was non significant difference between favorable and those with unfavorable outcome as regards CD44v6 (P=0.1) and there was no correlation between CD44 v6, HB level, platelet count, WBCs count, LDH level and B.M. blast cells in ALL patients.

Conclusion: CD44 but not CD44v6 expression can serve as a powerful prognostic marker in childhood ALL associated with bad prognosis. CD44 high expression identifies high risk subgroup.