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Background. Minimal residual disease (MRD) is an independent prognostic factor in acute lymphoblastic leukemia (ALL) in children. The immunological assessment of MRD cell count is based on aberrant immunophenotype of tumor lymphoblasts. However, in the case of ALL originating from T-lineage precursor cells (T-ALL) no clear aberrancy criteria have been defi ned, yet. Flow-cytometric MRD assessment in T-ALL can be based on characteristics of normal T-cell ontogenesis, i.e. the absence of normal T-lineage precursor cells (T-LP) in bone marrow. Aim. To assess the feasibility of immunological method of fl ow cytometry for MRD detection based on T-LP immunophenotype on Days 15 and 33 of treatment of T-ALL children. Materials & Methods. The analysis included the data on primary immunophenotype and MRD assessment on Dayы 15 and 33 of treatment of 31 T-ALL patients in the age of 2–17 years. In the majority of cases (61.3 %) the cortical/ thymic immuno-subvariant of ALL was detected, in the rest of cases (38.7 %) it was the pre-T-cell one. Diagnosis was based on cumulative results of morphocytochemical and immunological bone marrow analyses. Assessing the MRD state the morphological and immunological analyses of bone marrow aspirate were carried out in parallel with one and the same tube. All patients enrolled in the trial were treated at Scientifi c Research Institute of Pediatric Oncology and Hematology of NN Blokhin National Medical Cancer Research Center according to the ALL IC-BFM 2009 protocol. Results. Our study demonstrated that at all therapy stages MRD can be assessed by the unifi ed immunological method based on detecting cyCD3+CD7+/++smCD3– (T-LP) immunophenotype cells. It is important to ensure that the correct clones of monoclonal antibodies are used for detecting CD3 cytoplasmic and membrane molecules (UCHT1 and SK7, respectively). Standard risk group included no patients. The majority of patients (76.2 %) treated according to ALL ICBFM 2009 protocol were assigned to medium risk group on 80 О.А. Чернышева и др. КЛИНИЧЕСКАЯ ОНКОГЕМАТОЛОГИЯ Большинство пациентов (76,2 %), проходивших лечение по протоколу ALL IC-BFM 2009, составили группу промежуточного риска на 15-й день терапии. К 33-му дню 25 % из них перешли в группу высокого риска. Заключение. Возможности многоцветной проточной цитометрии позволяют наиболее полно охарактеризовать первичный иммунофенотип опухолевых Т-лимфобластов для дальнейшего поиска лейкоз-ассоциированных иммунофенотипов. Благодаря особенностям онтогенеза нормальных Т-клеток можно унифицировать иммунологические подходы к оценке МОБ на всех этапах терапии Т-ОЛЛ. Ключевые слова: Т-линейные острые лимфобластные лейкозы, многоцветная проточная цитометрия, минимальная остаточная болезнь, лейкоз-ассоциированный иммунофенотип. Получено: 21 июня 2018 г. Принято в печать: 18 декабря 2018 г. Для переписки: Ольга Алексеевна Чернышева, Каширское ш., д. 24, Москва, Российская Федерация, 115478; тел.: +7(499)324-14-30; e-mail: beznos.olga@gmail.com Для цитирования: Чернышева О.А., Гривцова Л.Ю., Серебрякова И.Н. и др. Диагностика острых лимфобластных лейкозов из Т-линейных предшественников и подходы к мониторингу минимальной остаточной болезни. Клиническая онкогематология. 2019;12(1):79–85. DOI: 10.21320/2500-2139-2019-12-1-79-85 Day 15 of treatment. By Day 33 a quarter of them (25 %) was included into high risk group. Conclusion. The capabilities of multicolor fl ow cytometry allow for the most complete characterization of primary immunophenotype of tumor T-cell lymphoblasts for further search of leukemia-associated immunophenotypes. Specifi c ontogenesis features of normal T-cells enable unifi cation of immunological approaches to MRD assessment at all stages of T-ALL therapy.

Diagnosis of Acute Lymphoblastic Leukemia Originating From T-Lineage Precursors and Approaches to Minimal Residual Disease Monitoring