The purpose of this work was evaluation of prognostic significance of 11q23/KMT2A rearrangements in infants (aged under 365 days) with B-cell precursor acute lymphoblastic leukemia (ALL) enrolled in Russian-Belarus multicenter trial MLLBaby. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Research Institute of Medical Cell Technologies (Ekaterinburg). Various 11q23/KMT2A rearrangements were revealed in 100 (72%) of 139 patients. Event-free survival (EFS) in the intermediate risk group of MLL-Baby trial was 35.1% (standard error (SE) 6.9%), in the high risk group – 38.3% (SE 7.1%) (p = 0.941). The most unfavorable prognosis had infants with translocation t(9;11)/KMT2A-MLLT3: EFS 18.8% (SE 9.8%), cumulative incidence of relapse (CIR) 75.0% (SE 9.7%). Intermediate results were obtained in patients with translocations t(4;11)/KMT2A-AFF1 and t(11;19)/KMT2A-MLLT1: EFS 36.9% (SE 7,2%) and 32,7% (SE 10.4%), respectively; CIR 46.3% (SE 7.8%) and 50.9% (SE 12.3%). The most favorable treatment outcome was achieved in infants carrying translocation t(10;11)(p12;q23)/KMT2A-MLLT10: EFS 83.3% (SE 15.2%), CIR 0,0%. In the multivariate analysis unfavorable outcome of KMT2A-rearranged infant ALL was associated with initial CNS involvement (p = 0.020), initial white blood cell count higher than 300 × 109 /L (p = 0.028), more than 5% blast cells on day 15 in bone marrow (p = 0.012) and presence of translocation t(11;19)/KMT2A-MLLT1 (p = 0.012).

Aim. The objective of the study was searching for surface antigen expression that could predict presence of translocation t(12;21)(p13;q22)/ ETV6-RUNX1 in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients. Results. ETV6-RUNX1 fusion gene transcript was revealed in 72 (21.1%) out of 341 children with BCP-ALL. Leukemic blast cells in ETV6-RUNX1 — positive patients more frequently had high CD10 expression, myeloid markers co-expression, including CD13, CD33, CD117, and absence of CD20 than in ETV6-RUNX1 — negative ones. Nevertheless diagnostic test performance characteristics of each single parameter was not strong enough for predicting the presence of translocation t(12;21)(p13;q22)/ETV6-RUNX1. On the second step of analysis we used various combinations of the above mentioned markers. The highest diagnostic test performance parameters were obtained in case of combination of high CD117 and heterogeneous CD34 expressions. Specificity of this combination was 0.996 (95% CI 0.989-1.000), positive predictive value 0.947 (95% CI 0.847- 1.000), positive likelihood ratio 67.250 (95% CI 9.130-495.348), while negative likelihood ratio was 0.752 (95% CI 0.659-0.860). Conclusion. Thus, combination of CD34 heterogeneous expression and CD117 expression is highly specific for translocation t(12;21)(p13;q22)/ ETV6-RUNX1. However this combination had limited applicability, because it revealed in 25.0% percent of patients only.

This article represents results of work of Center of pediatric oncology and hematology of Regional pediatric clinical hospital № 1 of Yekaterinburg on Hematopoietic stem cell transplantation (HSCT) during the period 2006–2016. One hundred seventeen HSCT performed during this time including 70 autologous, 33 allogenic, 14 haploidentical at patients with solid tumors (n = 55), acute leukemias (n = 27), lymphomas (n = 9), non-malignant diseases (n = 11). Results of treatment depending on type of disease and HSCT were shown. It was indicated that presence of minimal residual disease (MRD) before HSCT in case of leukemia and neuroblastoma was indicated as negative prognosis. Possible way of treatment of persistent MRD after HSCT with the help of blinatumomab and donor lymphocytes infusion showed.

We performed clinical and laboratory characterization of patients with rare translocation t(1;11)(p32;q23) leading to MLL-EPS15 fusion gene formation. Study cohort consisted of 33 primary acute leukemia (AL) cases including 6 newly diagnosed and 27 patients previously described in literature. Among study group patients t(1;11)(p32;q23) was found most frequently in infant AL cases (median age 8 months). In acute lymphoblastic leukemia (ALL) male/female ratio was 1:3, in acute myeloid leukemia (AML) it was 1:1. Additional cytogenetic aberrations in 38 % of patients were revealed. The most frequent breakpoint position in EPS15 gene was intron 1. Four different types of MLLEPS15 fusion gene transcripts were detected. Primers-probe-plasmid combination for MLL-EPS15 fusion gene transcript monitoring by realtime quantitative polymerase chain reaction (RQ-PCR) was developed and successfully applied. In 3 patients RQ-PCR was done on genomic DNA for absolute quantification of MLL-EPS15 fusion gene. High qualitative concordance rate (92 %) was noted between minimal residual disease data obtained in cDNA and genomic DNA for MLL-EPS15 fusion detection.

The mechanisms of chimeric gene formation with MLL gene involvement in infants aged under 1 year, suffering from acute leukemia, are described. Rearrangement of MLL gene in DNA was detected in the patients by long inverted polymerase chain reaction (LI-PCR). The study was carried out in 72 patients aged 1 day to 11 months, 52 of these with acute lymphoblastic leukemia (ALL), 19 with acute myeloid leukemia (AML), and 1 with acute undifferentiated leukemia. The most incident (53.8%) chimeric gene in ALL was MLL-AF4; other ones were more rare: MLL-MLLT7 (23.1%), MLL-MLLT3 (13.5%), MLL-EPS15 (7.7%), and MLL-AFF3 (1.9%). In AML the most incident (36.8%) chimeric gene was MLL-MLLT3; other chimeric genes were MLL-MLLT10 (26.3%), MLL-MLLT11 and MLL-MYO1F (10.5% each), MLL-AF4, MLL-SEPT6, and MLL-SEPT9 (5.3% each). The most frequent aberration zone in MLL gene DNA was intron 11(48.1% cases) in ALL and intron 9 (42.1%) in AML. Patients with ALL with the rupture site in intron 11 were the youngest (p = 0.025). No relationship between the location of rupture sites and patient's gender, initial leukemia level, and partner gene type was detected. The aberration zones in MLL partner genes most often involved one or two introns, except AF4 and MLLT10 genes, in which the aberration zones were longer. The most incident mechanism of chimeric gene formation with MLL participation was reciprocal translocation (73.6%), trans-splicing or insertions were significantly more rare (15.3 and 11.1%, respectively). Rare MLL partner genes were found by LI-PCR: AFF3, MYO1F, SEPT6, SEPT9, as well as atypical locations of ruptures in the presence of MLL-AF4: MLL gene intron 7 and AF4 gene intron 10, not detected by the standard reverse transcription PCR. Hence, we characterized in detail the structure of chimeric genes with MLL participation in a large group of infants aged under 1 year, suffering from acute leukemia.