SIGNIFICANCE OF ETV6-RUNX1 FUSION GENE TRANSCRIPT DETECTION IN PEDIATRIC B-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA WITH TRANSLOCATION t(12;21)(p13;q22)

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Abstract

Introduction. Translocation t(12;21)(p13;q22) is one of the most common structural genetic abnormalities in childhood acute lymphoblastic leukemia (ALL). It cannot be detected by conventional G-banding, so a reverse-transcriptase polymerase chain reaction (RT-PCR) or fluorescent in situ hybridization are used for this purpose.

The aim of the study was to evaluate the prognostic significance of qualitative and quantitative detection of ETV6-RUNX1 fusion gene transcript at various time points in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients.

Materials and methods. ETV6-RUNX1 fusion gene transcript was revealed by both reverse-transcriptase PCR and quantitative real-time PCR (RQ-PCR) in 34 out of 166 (20.5 %) children with BCP-ALL. Qualitative ETV6-RUNX1-positivity at days 36 and 85 led to unfavorable outcome (lower event-free survival –EFS and higher cumulative incidence of relapse – CIR). While ETV6-RUNX1 status at day 15 did not allow to divide patients with different outcomes. By ROC curve analysis we determined threshold levels (TL) for ETV6-RUNX1/ABL1 ratio at days 0, 15, 36 and 85. Afterwards we adjusted obtained results to 10-fold scale.

Results. So practically applicable TL were as follows 500.0 %, 1 %, 0.1 % и 0.01 % for days 0, 15, 36 and 85, respectively. EFS and CIR were both worse in patients with ETV6-RUNX1/ABL1 ratio equal or above defined TL. Moreover, initial ratio ≥500,0 % corresponded to delayed blast clearance at days 15 and 36. We showed good qualitative (84.8 %) and quantitative (R2 = 0.953) concordance between ETV6-RUNX1/ABL1 ratio and MRD data obtained by flow cytometry at days 15, 36, 85. Of note, defined TL for ETV6-RUNX1/ABL1 at days 15, 36, 85 were equal to prognostically important levels for flow cytometry MRD.

Conclusion. Thus, qualitative detection and quantitative value of ETV6-RUNX1 fusion gene transcript showed prognostic significance in the course of treatment in children with BCP-ALL. Based on these results we propose standardization approaches for Moscow – Berlin ALL study group.

About the authors

G. A. Tsaur

Sverdlovsk Regional Children’s Hospital No 1; Center for Specialized Types of Medical Care “Institute of Medical Cell Technologies”; Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences; Ural State Medical University, Ministry of Health of Russia

Author for correspondence.
Email: tsaur@mail.ru

32 Serafimy Deryabinoy St., Ekaterinburg 620149; 22A Karlа Marksа St., Ekaterinburg 620026; 106 Pervomayskaya St., Ekaterinburg 620049; 3 Repina St., Ekaterinburg 620030

Russian Federation

Т. О. Riger

Sverdlovsk Regional Children’s Hospital No 1; Center for Specialized Types of Medical Care “Institute of Medical Cell Technologies”

32 Serafimy Deryabinoy St., Ekaterinburg 620149; 22A Karlа Marksа St., Ekaterinburg 620026

Russian Federation

A. M. Popov

Dmitriy Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology

1 Samory Mashela Sr., Moscow 117997

Russian Federation

T. Yu. Verzhbitskaya

Sverdlovsk Regional Children’s Hospital No 1; Center for Specialized Types of Medical Care “Institute of Medical Cell Technologies”

32 Serafimy Deryabinoy St., Ekaterinburg 620149; 22A Karlа Marksа St., Ekaterinburg 620026

Russian Federation

L. V. Vakhonina

Sverdlovsk Regional Children’s Hospital No 1; Center for Specialized Types of Medical Care “Institute of Medical Cell Technologies”

32 Serafimy Deryabinoy St., Ekaterinburg 620149; 22A Karlа Marksа St., Ekaterinburg 620026

Russian Federation

A. A. Vlasova

Sverdlovsk Regional Children’s Hospital No 1

32 Serafimy Deryabinoy St., Ekaterinburg 620149

Russian Federation

Yu. V. Olshanskaya

Dmitriy Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology

1 Samory Mashela Sr., Moscow 117997

Russian Federation

А. N. Kazakova

Dmitriy Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology

1 Samory Mashela Sr., Moscow 117997

Russian Federation

O. V. Streneva

Sverdlovsk Regional Children’s Hospital No 1; Center for Specialized Types of Medical Care “Institute of Medical Cell Technologies”

32 Serafimy Deryabinoy St., Ekaterinburg 620149; 22A Karlа Marksа St., Ekaterinburg 620026

Russian Federation

O. V. Makarova

Sverdlovsk Regional Children’s Hospital No 1

32 Serafimy Deryabinoy St., Ekaterinburg 620149

Russian Federation

S. V. Tsvirenko

Sverdlovsk Regional Children’s Hospital No 1; Ural State Medical University, Ministry of Health of Russia

32 Serafimy Deryabinoy St., Ekaterinburg 620149; 3 Repina St., Ekaterinburg 620030

Russian Federation

L. I. Saveliev

Sverdlovsk Regional Children’s Hospital No 1; Center for Specialized Types of Medical Care “Institute of Medical Cell Technologies”; Ural State Medical University, Ministry of Health of Russia

32 Serafimy Deryabinoy St., Ekaterinburg 620149; 22A Karlа Marksа St., Ekaterinburg 620026; 3 Repina St., Ekaterinburg 620030 Russian Federation

О. R. Arakaev

Sverdlovsk Regional Children’s Hospital No 1; Center for Specialized Types of Medical Care “Institute of Medical Cell Technologies”

32 Serafimy Deryabinoy St., Ekaterinburg 620149; 22A Karlа Marksа St., Ekaterinburg 620026

Russian Federation

L. G. Fechina

Sverdlovsk Regional Children’s Hospital No 1; Center for Specialized Types of Medical Care “Institute of Medical Cell Technologies”

32 Serafimy Deryabinoy St., Ekaterinburg 620149; 22A Karlа Marksа St., Ekaterinburg 620026

Russian Federation

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