Translocation t(12;21)(p13;q22)/ETV6::RUNX1 is among the most common genetic aberrations in pediatric B-cell precursor acute lymphoblastic leukekian (BCP-ALL). This translocation is often combined with ETV6 and/or RUNX1 copy number variations. Fluorescence in situ hybridization (FISH) technique, which is widely used to reveal the presence of t(12;21)(p13;q22), also allows the detection of these additional genetic aberrations (FISH patterns). The aim of this study was to provide detailed characteristics of FISH patterns in patients with BCP-ALL and the t(12;21)(p13;q22)/ETV6::RUNX1 translocation. In our study we enrolled 241 patients with t(12;21)-positive ALL who had undergone testing with a dual-color double-fusion FISH assay between 2008 and 2023. This study was approved by the Independent Ethics Committee and the Academic Council of the Research Institute of Medical Cell Technologies (Ekaterinburg). A single FISH pattern (monoclonal cases) was identified in 200 patients (83.0%), 2 or more patterns (polyclonal cases) were detected in 41 (17.0%) patients. The majority of polyclonal cases (n = 39; 95.1%) exhibited 2 patterns. The most common secondary genetic alteration was ETV6 deletion (n = 105; 43.5%). Less common aberrations included an additional copy of RUNX1 (n = 97; 40.2%), a combination of ETV6 deletion and an additional copy of RUNX1 (n = 27; 11.2%), and an additional copy of ETV6 (n = 5; 2.0%). The number of the patients with one FISH pattern that did not contain any additional genetic aberrations as a result of a reciprocal translocation (2F1G1R) was relatively small (n = 35; 17.5%). We identified 5 prognostically unfavorable FISH patterns associated with a high risk of relapse. These included cases with simultaneous presence of ETV6 and RUNX1 additional copies (pattern 2F2G2R), isolated additional copies of RUNX1 (pattern 2F2R-3F2R) or ETV6 (pattern 1F1G2R-2F2G4R), a partial deletion of ETV6 (pattern 2F1Gdim1R) and a non-reciprocal translocation of t(12;21) (pattern 1F1R-1F1G1R). Grouping these unfavorable prognostic FISH patterns together made it possible to predict 6 (46%) out of 13 relapses that occurred in the patients during the study period. It is important to highlight that the number of the patients with unfavorable FISH patterns and initial leukocytosis of > 30 × 109 leukocytes/L did not differ significantly from the rest of the group. Another important observation was that the patients with prognostically unfavorable FISH patterns responded well to induction therapy, as assessed both by cytological examination of blood and bone marrow smears on days 8, 15, and 36 of therapy and by MRD response at the end of induction therapy according to the ALL-MB 2015 protocol. A comparison of FISH patterns detected at initial diagnosis and at relapse showed that only 6 (50%) out of 12 cases who had undergone FISH testing at both time points remained stable. In conclusion, BCP-ALL with the translocation t(12;21)(p13;q22)/ETV6::RUNX1 was characterized by a vast variety of secondary genetic aberrations detected by FISH, the most prevalent of which was ETV6 deletion. A group of unfavorable FISH patterns identified in our study warrants further investigation in a larger cohort of ALL patients for their possible re-stratification so that they could receive more intensive treatment.

The use of all-trans retinoic acid (ATRA) drastically improved the results of therapy for acute promyelocytic leukeimia (APL). The high efficiency of the Russian protocol APL-93—98 applied to 62 children and adolescents with APL (event-free and overall survival (EFS and OS) were 84±5% respectively with a relapse rate of 7%) was achieved, by administering the high cumulative dose of daunoruicin (495 mg/m2) and single doses of АТRА (45 mg/m2). In this connection, the APL-2003 protocol attempted to reduce both acute and chronic toxicity of the therapy, by decreasing the cumulative dose of daunorubicin to 405 mg/m2 and the single dose of АТRА to 25 mg/m2 under regular control of minimal residual disease via molecular monitoring of the specific transcript PML/RARα. Analysis of the results of treatment in 61 patients aged 1.3 to 17 years (median 11.3) showed that despite of the reduced protocol intensity, the efficiency of therapy did not generally reduce — EFS and OS were 79±6 and 93±3%, respectively. The likelihood of the development of a relapse was significantly affected by molecular resistance, i.e. the retention of the transcript PML/RARα before a phase of maintenance therapy: the recurrence risk in this group was 57% whereas there were no differences in all cure rates between the patients depending on baseline leukocytosis. All 6 patients with relapses were treated with arsenic trioxide, resulting in not only clinical and hematological, but also molecular remissions; thereafter the patients received myeloablative therapy and autologous hemopoietic stem cell transplantation. The second remission lasted 3 to 24 months. Thus, reducing the cumulative dose of anthracyclines and the dose of АТRА did not make the results of the therapy for APL worse. The monitoring of minimal residual disease before and during maintenance therapy is a mandatory component of successful treatment in APL patients. Arsenic trioxide is an effective agent for the treatment of APL relapses.

ЦЕЛЬ ИССЛЕДОВАНИЯ Оценить возможность прогнозирования наличия транслокации t(12;21)(p13;q22)/ETV6::RUNX1 методом проточной цитометрии с использованием антигенов CD27 и CD44 у детей с острым лимфобластным лейкозом из B-линейных предшественников (ВП-ОЛЛ). МЕТОДЫ ИССЛЕДОВАНИЯ В исследование вошло 437 случаев ВП-ОЛЛ у детей в возрасте от 1 до 18 лет. Процентное количество CD27 и CD44 позитивных опухолевых клеток, а также средняя интенсивность флуоресценции (MFI) были сопоставлены с результатами молекулярно-генетических методов исследования. Оптимизация порогового уровня для определения позитивной экспрессии антигенов CD27 и CD44 была проведена с помощью ROC-анализа. РЕЗУЛЬТАТЫ Было доказано, что транслокация t(12;21)(p13;q22)/ETV6::RUNX1 ассоциирована с сочетанием позитивной экспрессии CD27 и сниженной, либо отсутствующей экспрессией CD44. Тем не менее, оптимальными пороговыми уровнями для определения позитивной экспрессии CD27 и CD44 в процентах оказались 80,7 и 86,1% соответственно. Использование отношения MFI CD27 к MFI CD44 показало наиболее высокий параметр диагностического отношения шансов — 953,1. ЗАКЛЮЧЕНИЕ Использование сочетания антигенов CD27 и CD44 позволило с высокой диагностической эффективностью предсказывать наличие t(12;21)(p13;q22)/ETV6::RUNX1 при ВП-ОЛЛ у детей методом проточной цитометрии.

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).

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.

The objective of the study was searching for surface antigen expression that could predict presence of translocation t(12;21)(p13;q22)/ETV6RUNX1 in pediatric B-cell precursor acute lymphoblastic leukemia patients.Results . ETV6-RUNX1 fusion gene transcript was revealed in 118 (22.4 %) out of 526 children with B-cell precursor acute lymphoblastic leukemia. 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.Conclusion . Thus application of conventional set of immunological markers does not allow reliable distinguishing this patients’ subgroup. However antibodies panel enlargement, high degree of flow cytometry standardization and additional analytical methods can potentially improve applicability of antigen profile analysis for separation of patients with translocation t(12;21)(p13;q22)/ETV6-RUNX1.

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.

The purpose of the current work was the estimation of prognostic significance of cytogenetic and molecular markers, assessed by multiplex ligation-dependent probe amplification (MLPA) in 142 cases of pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients. Good-risk genetic (GEN-GR) group consisted of 114 patients carrying either ETV6-RUNX1 or high hyperdiploidy together with normal copy-number status for all 8 genes (IKZF1, PAX5, ETV6, RB1, BTG1, EBF1, CDKN2A/2B and PAR1) or isolated deletions affecting ETV6/ PAX5/BTG1 and ETV6 deletions with a single additional deletion of BTG1/PAX5/CDKN2A/2B. All other patients (n = 28) were classified to genetic poor risk (GEN-PR) group. GEN-PR features were older age (p = 0.015), stratification to high-risk group of ALL-MB 2008 protocol (p = 0.001), higher initial WBC (p = 0.008), M3 marrow status on day 15 (p = 0.002) and lack of remission on day 36 (p = 0.039). GEN-PR patients had statistically significant lower event-free survival (EFS) (0.59 ± 0.11 vs 0.88 ± 0.03; p = 0.0008), overall survival (OS) (0.63 ± 0.15 vs 0.93 ± 0.02; p = 0.0050) and higher cumulative incidence of relapse (CIR) (0.38 ± 0.12 и 0.06 ± 0.02; p < 0.0001) in comparison to GEN-GR patients. Genetic risk group stratification retained its negative prognostic value in multivariate analysis affecting EFS (hazard ratio (HR) – 2.659; 95 % CI 1.047–6.755; p = 0.040) and CIR (HR – 3.864; 95 % CI 1.226–12.183; p = 0.021), nut did not influenced to OS (HR – 1.479; 95 % CI 0.356–6.139; p = 0.590). There was no prognostic significance of genetic risk group classifier in the “B-other ALL” group. Majority of unfavorable events (9 out of 10) and relapse (8 out of 9) in GEN-PR patients were revealed in case of IKZF1 deletion co-occurrence. Moreover all 15 patients carrying IKZF1 deletions were stratified to GEN-PR group. So when we added IKZF1 deletion as extra variable in the multivariate analysis genetic risk group classification lost its prognostic significance on EFS (HR – 0.696; 95 % CI 0.086–5.636; p = 0,735), and CIR (HR – 0.511; 95 % CI 0.053–4.924; p = 0.561), while IKZF1 deletion remained its prognostic value both to risk of unfavorable event (HR – 4.292; 95 % CI 1.521–12.911; p = 0.006) and risk of relapse (HR – 9.163; 95 % CI 3.131–26.815; p < 0.001). Thus, combination of cytogenetic risk group and MLPA markers did not bring any advantage over detection of isolated IKZF1 deletion for the estimation of prognosis in pediatric BCP-ALL.

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.

The occurrence of minimal residual disease is an important prognostic factor under acute lymphoblastic leucosis in children and adults. In overwhelming majority of research studies bone marrow is used to detect minimal residual disease. The comparative characteristic of detection of minimal residual disease in peripheral blood and bone marrow was carried out. The prognostic role of occurrence of minimal residual disease in peripheral blood and bone marrow under therapy according protocol MLL-Baby was evaluated. The analysis embraced 142 pair samples from 53 patients with acute lymphoblastic leucosis and various displacements of gene MLL younger than 365 days. The minimal residual disease was detected by force of identification of chimeric transcripts using polymerase chain reaction in real-time mode in 7 sequential points of observation established by protocol of therapy. The comparability of results of qualitative detection of minimal residual disease in bone marrow and peripheral blood amounted to 84.5%. At that, in all 22 (15.5%) discordant samples minimal residual disease was detected only in bone marrow. Despite of high level of comparability of results of detection of minimal residual disease in peripheral blood and bone marrow the occurrence of minimal residual disease in peripheral blood at various stages of therapy demonstrated no independent prognostic significance. The established differences had no relationship with sensitivity of method determined by value of absolute expression of gene ABL. Most likely, these differences reflected real distribution of tumor cells. The results ofstudy demonstrated that application ofperipheral blood instead of bone marrow for monitoring ofminimal residual disease under acute lymphoblastic leucosis in children of first year of life is inappropriate. At the same time, retention of minimal residual disease in TH4 in bone marrow was an independent andprognostic unfavorable factor under therapy of acute lymphoblastic leucosis of children offirst year of life according protocol MLL-Baby (OO=7.326, confidence interval 2.378-22.565).

Background & Aims. The diagnosis of chronic myeloid leukemia (CML) is confirmed in case of translocation t(9;22) (q34;q 11 ) is revealed by chromosomal banding analysis and/or BCR-ABL fusion gene transcript is detected by reverse-transcriptase polymerase chain reaction (RT-PCR). However, rare types of chimeric BCR-ABL transcript have been described and they may be overlooked. Moreover, timely CML diagnosing and detection of different types of BCR-ABL transcript are very important task, because the clinical course of the disease and efficacy of the therapy with tyrosine kinase inhibitors partly depend on the structure of BCR-ABL fusion. In some cases CML may be diagnosed without the chromosomal banding analysis and be confirmed by RT-PCR alone, so we consider it important to develop a diagnostic algorithm that allows to detect virtually all types of BCR-ABL fusion gene transcript. Methods. Over the period from January, 2004, till December, 2013, in the Molecular biology laboratory of Pediatric oncology and hematology center in Regional Chlildren’s Hospital # 1 (Yekaterinburg), the diagnosis of CML was confirmed in 1082 patients: 531 (49 %) males and 551 (51 %) females. The median age was 50 years (range 5-88 years). Chromosomal banding analysis and nested RT-PCR were performed in all patients. Reverse primers for nested RT-PCR are localized in exons 2 and 3 of ABL and are used for detection of all types of BCR-ABL transcript. Forward primes for typical e13a2 and e14a2 (M-bcr) transcripts are localized in exons 12 and 13 BCR gene, forward primes for e1a2 (m-bcr) transcript are complementary to exon 1 of BCR. While atypical amplicons are detected we performed Sanger sequencing with primers of the second round of RT-PCR and BigDye Terminator 3.1 kit. Results. Based on 1082 of confirmed CML cases we have developed a diagnostic strategy for detection of typical and atypical types of BCR-ABL fusion gene transcript in CML patients using RT-PCR. Proposed algorithm allowed to detect typical BCR-ABL transcript, e14a2 and e13a2, in 62.53 % and 35.89 % of cases, respectively. Atypical transcripts, e13a3, e14a3, e19a2, e1a2, e3a2, e6a2, and e8a2, were detected in 1.57 % of cases. Conclusion. Therefore, the proposed diagnostic algorithm proved to be effective for detection of typical and atypical types of BCR-ABL fusion gene transcripts in CML patients.

The occurrence of minimal residual disease is an important prognostic factor under acute lymphoblastic leucosis in children and adults. In overwhelming majority of research studies bone marrow is used to detect minimal residual disease. The comparative characteristic of detection of minimal residual disease in peripheral blood and bone marrow was carried out. The prognostic role of occurrence of minimal residual disease in peripheral blood and bone marrow under therapy according protocol MLL-Baby was evaluated. The analysis embraced 142 pair samples from 53 patients with acute lymphoblastic leucosis and various displacements of gene MLL younger than 365 days. The minimal residual disease was detected by force of identification of chimeric transcripts using polymerase chain reaction in real-time mode in 7 sequential points of observation established by protocol of therapy. The comparability of results of qualitative detection of minimal residual disease in bone marrow and peripheral blood amounted to 84.5%. At that, in all 22 (15.5%) discordant samples minimal residual disease was detected only in bone marrow. Despite of high level of comparability of results of detection of minimal residual disease in peripheral blood and bone marrow the occurrence of minimal residual disease in peripheral blood at various stages of therapy demonstrated no independent prognostic significance. The established differences had no relationship with sensitivity of method determined by value of absolute expression of gene ABL. Most likely, these differences reflected real distribution of tumor cells. The results of study demonstrated that application of peripheral blood instead of bone marrow for monitoring of minimal residual disease under acute lymphoblastic leucosis in children of first year of life is inappropriate. At the same time, retention of minimal residual disease in TH4 in bone marrow was an independent and prognostic unfavorable factor under therapy of acute lymphoblastic leucosis of children of first year of life according protocol MLL-Baby (OO=7.326, confidence interval 2.378-22.565).

Р е з ю м е. Целью данной работы являлось описание механизмов образования химерных генов с вовлечением гена MLL у детей первого года жизни, больных острыми лейкозами, у которых методом длинной инвертированной полимеразной цепной реакции (ДИ-ПЦР) в ДНК выявлена перестройка гена MLL. В исследование были включены 72 больных в возрасте от 1 дня до 11 мес, в том числе 52 больных острым лимфобластным лейкозом (ОЛЛ), 19 больных острым миелоидным лейкозом (ОМЛ), 1 больной острым недифференцированным лейкозом. При ОЛЛ наиболее частым (53,8%) химерным геном являлся MLL-AF4, реже выявлялись MLL-MLLT1 (23,1%), MLL-MLLT3 (13,5%), MLL-EPS15 (7,7%), MLL-AFF3 (1,9%). При ОМЛ самым часто выявляемым (36,8%) химерным геном был MLL-MLLT3, реже (26,3%) были найдены MLL-MLLT10, MLL-MLLT11 и MLL-MYO1F (по 10,5%), MLL-AF4, а также MLL-SEPT6 и MLL-SEPT9 (по 5,3%). Наиболее частой зоной разрыва в ДНК гена MLL при ОЛЛ являлся 11-й интрон, на долю которого приходилось 48,1% случаев, а при ОМЛ — это 9-й интрон (42,1%). Больные ОЛЛ, у которых точка разрыва располагалась в 11-м интроне, были младше всех остальных (p = 0,025). Не обнаружено связи между локализацией точек разрыва и полом больного, уровнем инициального лейкоцитоза и типом гена-партнера. Зоны разрыва в генах-партнерах MLL чаще всего затрагивали один или два интрона, за исключением генов AF4 и MLLT10, в которых зоны разрывов более протяженные. Самым частым механизмом образования химерных генов с участием MLL являлась реципрокная транслокация (73,6%), значительно реже — транс-сплайсинг (15,3%) или инсерции (11,1%). С помощью ДИ-ПЦР были найдены такие редкие гены-партнеры MLL, как AFF3, MYO1F, SEPT6, SEPT9, а также нетипичные локализации точек разрыва при наличии MLL-AF4: 7-й интрон гена MLL и 10-й интрон гена AF4, не выявляемые стандартной ПЦР с обратной транскрипцией. Таким образом, нами детально охарактеризована структура химерных генов с участием MLL в большой группе детей первого года жизни, больных острыми лейкозами. Ключевые слова : острый лейкоз; дети первого года жизни; перестройки гена MLL; полимеразная цепная реакция.

117 cases of infant acute lymphoblastic leukemia without Down syndrome (aged from 1 to 365 days) were included in the current study.Rearrangements of 11q23 (MLL) were revealed in 74 (63.2 %) patients. Among this group the most common rearrangement was t(4;11) q21;q23)/MLL-AF4 detected in 63.5 % cases, less frequently was found t(11;19)(q23;p13)/MLL-MLLT1 (in 18.9 % cases), t(10;11) p12;q23)/MLL-MLLT10 and t(1;11)(p32;q23)/ML L-EPS15 (each one in 6.8 %), t(9;11)(p22;q23)/MLL-MLLT3 in 2.7 %. Children under 6 months of age had significantly higher incidence of 11q23 (ML L) rearrangements in comparison with infants olde r than 6 months (84.0 % vs. 47.8 %, p < 0.001). P atients with translocations 11q23 (ML L) more frequently had BI-A LL and less frequently BII-ALL than children without these rearrangements (p < 0.001 f or both). Fusion gene transcript w as sequenced in 26 ML Lrearranged cases. Depending on breakpoint position within ML L and partner genes we detected 7 differ ent types of ML L-AF4 fusion gene transcript, 3 types of MLL-MLLT1, 2 types of MLL-EPS15. The most common fusion site within MLL gene was exon 11, detected in 14 (53.8 %) patients.