Prognostic significance of foetal-like tyrosine kinase 3 mutation in Egyptian children with acute leukaemia Y. AL-TONBARY*, A. K. MANSOUR*, H. GHAZY*, D. M. ELGHANNAM † , H. A. ABD-ELGHAFFAR † INTRODUCTION Foetal like tyrosine kinase 3 (Flt3) (fms-like tyrosine kinase-CD 135) also referred to as foetal liver kinase 2 or stem cell tyrosine kinase is a member of the class III tyrosine kinase receptor family that includes the c-kit, c-fms and PDGF receptors (Lyman & Jacobsen, 1998), located on chromosome 13q12, and composed of four domains; the extra cellular domains consisting of five immunoglobulin-like structures, the trans-membrane * Hematology/Oncology/BMT Unit, Mansoura University Children’s Hospital, Mansoura, Egypt † Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt Correspondence: Prof. Youssef Al-Tonbary, Hemato- logy/Oncology/BMT Unit, Manso- ura University Children’s Hospital, Mansoura, Egypt. Tel.: +2012 3165302; Fax: +2050 2262307; E-mail: ytonbary@gmail.com doi:10.1111/j.1751-553X.2008.01039.x Received 18 August 2007; accepted for publication 20 December 2007 Keywords Acute leukemia, Flt3, prognosis SUMMARY The foetal like tyrosine kinase 3 mutation (Flt3) gene encodes a tyrosine kinase receptor that regulates proliferation and differentiation of haematopoietic stem cells. In children with acute myelogenous leukaemia (AML), internal tandem duplication of the Flt3 gene (Flt3/ ITD) was previously reported and correlated to poor prognosis. Limited data are available about childhood acute lymphoblastic leukaemia (ALL). We analysed bone marrow specimens from 55 newly diagnosed acute leukaemia cases including 30 AML and 25 ALL by genomic PCR for the presence of Flt3/ITD and correlated its presence with clinical outcome. Tandem duplication was found in 6/30(20%) AML cases: 2/8 M1, 1/8 M2, 2/6 M3, 1/6 M4 with loss of heterozygosity (LOH) in two cases. Four of the cases with duplication were males and the other two cases were females. Complete remission was achieved in 16.6% of cases with duplication vs. 45.8% in cases without duplication. Failure to achieve induction remission was noted in 50% of cases with duplication vs. 29.1% in cases without duplication. FLt3/ITD was not found in ALL cases. Lineage restriction analysis revealed that Flt3/ITD was not present in lymphocytes, suggesting a lack of stem cell involvement for this mutation. Flt3/ITD was the most significant prognostic factor as declared by multivariate analysis. Patients with Flt3/ITD appear to be refractory to primary induction therapy, and for those who achieve remission, there is a high rate of relapse and death so there may be an association between this type of mutation and patient outcome. ORIGINAL ARTICLE INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY Ó 2008 The Authors 320 Journal compilation Ó 2008 Blackwell Publishing Ltd, Int. Jnl. Lab. Hem. 2009, 31, 320–326