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Prognostic significance of foetal-like tyrosine kinase 3 mutation in Egyptian children with acute leukaemia.
Int J Lab Hematol. 2009 Jun; 31(3):320-6.IJ

Abstract

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.

Authors+Show Affiliations

Hematology/Oncology/BMT Unit, Mansoura University Children's Hospital, Mansoura, Egypt. ytonbary@gmail.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18336585

Citation

Al-Tonbary, Y, et al. "Prognostic Significance of Foetal-like Tyrosine Kinase 3 Mutation in Egyptian Children With Acute Leukaemia." International Journal of Laboratory Hematology, vol. 31, no. 3, 2009, pp. 320-6.
Al-Tonbary Y, Mansour AK, Ghazy H, et al. Prognostic significance of foetal-like tyrosine kinase 3 mutation in Egyptian children with acute leukaemia. Int J Lab Hematol. 2009;31(3):320-6.
Al-Tonbary, Y., Mansour, A. K., Ghazy, H., Elghannam, D. M., & Abd-Elghaffar, H. A. (2009). Prognostic significance of foetal-like tyrosine kinase 3 mutation in Egyptian children with acute leukaemia. International Journal of Laboratory Hematology, 31(3), 320-6. https://doi.org/10.1111/j.1751-553X.2008.01039.x
Al-Tonbary Y, et al. Prognostic Significance of Foetal-like Tyrosine Kinase 3 Mutation in Egyptian Children With Acute Leukaemia. Int J Lab Hematol. 2009;31(3):320-6. PubMed PMID: 18336585.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prognostic significance of foetal-like tyrosine kinase 3 mutation in Egyptian children with acute leukaemia. AU - Al-Tonbary,Y, AU - Mansour,A K, AU - Ghazy,H, AU - Elghannam,D M, AU - Abd-Elghaffar,H A, Y1 - 2008/03/10/ PY - 2008/3/14/pubmed PY - 2009/8/1/medline PY - 2008/3/14/entrez SP - 320 EP - 6 JF - International journal of laboratory hematology JO - Int J Lab Hematol VL - 31 IS - 3 N2 - 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. SN - 1751-553X UR - https://www.unboundmedicine.com/medline/citation/18336585/Prognostic_significance_of_foetal_like_tyrosine_kinase_3_mutation_in_Egyptian_children_with_acute_leukaemia_ L2 - https://doi.org/10.1111/j.1751-553X.2008.01039.x DB - PRIME DP - Unbound Medicine ER -