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ctt-journal > Vinogradov et al. (Abstract)

Vinogradov et al. (Abstract)

Cellular Therapy and Transplantation (CTT), Vol. 3, No. 12
doi: 10.3205/ctt-2011-No12-abstract46

© The Authors. This abstract is provided under the following license: Creative Commons Attribution 3.0 Unported

Abstract accepted for "5th Raisa Gorbacheva Memorial Meeting Hematopoietic Stem Cell Transplantation in Children and Adults", Saint Petersburg, Russia, September 18–20, 2011

Preliminary Program

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A comparative analysis of TP53 gene mutations in acute myeloid and lymphoblastic leukemia patients

Alexander V. Vinogradov, Alexey V. Rezaikin, Alexander G. Sergeev, Tatiana S. Konstantinova, Julia V. Sveshnikova, Leonid N. Sharov, Natalia V. Vinogradova

Ural State Medical Academy, Sverdlovsk Regional Clinical Hospital N1, Ekaterinburg, Russia

Correspondence: Alexander V. Vinogradov, Ural State Medical Academy, 3, Repina str., 620028, Ekaterinburg, Russia, E-mail: vinogradov-av@spam is badrussia.ru

Abstract

Aim: To estimate the frequency and structural characteristics of TP53 gene mutations in acute myeloid (AML) and lymphoblastic leukemia (ALL) patients by using sequencing methods.

Patients and methods: 46 patients were included in study (AML 35, ALL 11). A total of 35 AML pts according to FAB variants were M0: 1, M1: 4, M2: 15, M2baso: 2, M3: 3, M4: 8, M4eo: 1, and acute myelofibrosis: 1. The distribution of ALL pts by immunophenotype was as follows: BI — 4, BII — 6, and TI — 1.

TP53 gene point mutation detection was studied using the sequencing method. The extraction of mRNA was made from bone marrow and peripheral blood neoplastic cells. Sequences of primers for TP53 gene amplification (exons 4–11) using a polymerase chain reaction and for the termination reaction for amplified loci were described in our previous report (http://www.ctt-journal.com/3-9-en-vinogradov-ea-2010jun28.html). Sequencing was realized using an automatic genetic analyzer ABI Prism 310 using reactive components and an ABI Prism BigDye Terminator Cycle Sequencing Kit v. 3.0 (Applied Biosystem, USA).

Results: Twenty-nine AML patients from the research group showed nucleotide substitution C215G (cytosine for guanine in position 215), which leads to a change of amino acid proline for arginine in position 72 (P72R) in the determining protein. Wild type TP53 (according to NM_000546, GenBank NCBI) was detected in 5 cases. Frame-shift deletion for thymidine in position 645 plus C215G and non-synonymous substitution G841C (D281H) were detected in 2 AML M2 pts with complex karyotype lesions (47, XY, del(3)(p12), del(5)(q31), add(17)(p13), -7, +21, +mar and 42, X, addi(1)(q31), addi(12)(q24), del(15)(p12), addi(16)(p13), del(18)(p12), -3, -9, -13, -X). ALL patients except 2 cases with BI showed polymorphic change C215G (7 cases) and TP53 wt (2 cases) as well. Non-synonymous nucleotide substitutions A736G (M246V) and G527T (C176F) were detected in 2 ALL BI pts with diploid karyotype.

Conclusion: TP53 gene mutations in acute myeloid leukemia were detected in pts with complex karyotype abnormalities, and in the diploid karyotype in the case of acute lymphoblastic leukemia.

Keywords: TP53 gene, sequencing, acute leukemia, point mutations