Cytogenetic and molecular genetic diagnostics in oncohematological disorders: a position paper of the Organization of Molecular Geneticists in Oncology and Oncohematology

Tsaur, Grigory; Olshanskaya, Yu. V.; Obukhova, Tatiana N.; Sudarikov, Andrey; Лазарева, О. В.; Гиндина, Т. Л.

doi:10.35754/0234-5730-2023-68-1-129-143

Cited by 7 publications

(2 citation statements)

References 41 publications

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“…In our primary cohort, BCL11B rearrangement was the most frequent recurrence event, occurring in 10 of 60 ETP-ALL cases. We also observed translocations involving ETV6 , RUNX1 , KMT2A , and MLLT10 , which are miscellaneous transcription factors and epigenetic regulators involved in definitive hematopoiesis [ 27 , 28 , 29 ]. Thus, their disruption intrinsically blocks the differentiation of early progenitor cells and promotes the leukemic phenotype throughout multiple AL subtypes [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Immunophenotypic but Not Genetic Changes Reclassify the Majority of Relapsed/Refractory Pediatric Cases of Early T-Cell Precursor Acute Lymphoblastic Leukemia

Demina,

Dagestani,

Borkovskaia

et al. 2024

IJMS

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Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) develops from very early cells with the potential for both T-cell and myeloid differentiation. The ambiguous nature of leukemic blasts in ETP-ALL may lead to immunophenotypic alterations at relapse. Here, we address immunophenotypic alterations and related classification issues, as well as genetic features of relapsed pediatric ETP-ALL. Between 2017 and 2022, 7518 patients were diagnosed with acute leukemia (AL). In addition to conventional immunophenotyping, karyotyping, and FISH studies, we performed next-generation sequencing of the T-cell receptor clonal repertoire and reverse transcription PCR and RNA sequencing for patients with ETP-ALL at both initial diagnosis and relapse. Among a total of 534 patients diagnosed with T-cell ALL (7.1%), 60 had ETP-ALL (11.2%). Ten patients with ETP-ALL experienced relapse or progression on therapy (16.7%), with a median time to event of 5 months (ranging from two weeks to 5 years). Most relapses were classified as AL of ambiguous lineage (n = 5) and acute myeloid leukemia (AML) (n = 4). Major genetic markers of leukemic cells remained unchanged at relapse. Of the patients with relapse, four had polyclonal leukemic populations and a relapse with AML or bilineal mixed-phenotype AL (MPAL). Three patients had clonal TRD rearrangements and relapse with AML, undifferentiated AL, or retention of the ETP-ALL phenotype. ETP-ALL relapse requires careful clinical and laboratory diagnosis. Treatment decisions should rely mainly on initial examination data, taking into account both immunophenotypic and molecular/genetic characteristics.

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Section: Discussionmentioning

confidence: 99%

Immunophenotypic but Not Genetic Changes Reclassify the Majority of Relapsed/Refractory Pediatric Cases of Early T-Cell Precursor Acute Lymphoblastic Leukemia

Demina,

Dagestani,

Borkovskaia

et al. 2024

IJMS

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“…As already described, the patients were divided into standard risk (SR) and intermediate risk (ImR) ( online supplemental figure S1 ) 9 10 and received the normal risk-adapted induction therapy in accordance with the ALL-MB protocol 2015 ( figure 1 ). 11 Before treatment, a centralized and standardized diagnosis including cytomorphology, immunophenotyping 12 and cyto- and molecular genetics 13 were routinely carried out in all patients. Using multicolor flow cytometry (MFC), MRD was measured at EOI, immediately after the treatment with blinatumomab and then four times at 3-month intervals during maintenance therapy ( figure 1 ).…”

Section: Methodsmentioning

confidence: 99%

Blinatumomab as postremission therapy replaces consolidation and substantial parts of maintenance chemotherapy and results in stable MRD negativity in children with newly diagnosed B-lineage ALL

Mikhailova,

Popov,

Roumiantseva

et al. 2024

J Immunother Cancer

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The bispecific T cell-binding antibody blinatumomab (CD19/CD3) is widely and successfully used for the treatment of children with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Here, we report the efficacy of a single course of blinatumomab instead of consolidation chemotherapy to eliminate minimal residual disease (MRD) and maintain stable MRD-negativity in children with primary BCP-ALL.Between February 2020 and November 2022, 177 children with non-high-risk BCP-ALL were enrolled in the ALL-MB 2019 pilot study (NCT04723342). Patients received the usual risk-adapted induction therapy according to the ALL-MB 2015 protocol. Those who achieved a complete remission at the end of induction (EOI) received treatment with blinatumomab immediately after induction at a dose of 5 μg/m2/day for 7 days and 21 days at a dose of 15 μg/m2/day, followed by 12 months of maintenance therapy. MRD was measured using multicolor flow cytometry (MFC) at the EOI, then immediately after blinatumomab treatment, and then four times during maintenance therapy at 3-month intervals.All 177 patients successfully completed induction therapy and achieved a complete hematological remission. In 174 of these, MFC-MRD was measured at the EOI. 143 patients (82.2%) were MFC-MRD negative and the remaining 31 patients had varying degrees of MFC-MRD positivity.MFC-MRD was assessed in all 176 patients who completed the blinatumomab course. With one exception, all patients achieved MFC-MRD negativity after blinatumomab, regardless of the MFC-MRD score at EOI. One adolescent girl with high MFC-MRD positivity at EOI remained MFC-MRD positive. Of 175 patients who had completed 6 months of maintenance therapy, MFC-MRD data were available for 156 children. Of these, 155 (99.4%) were MFC-MRD negative. Only one boy with t(12;21) (p13;q22)/ETV6::RUNX1became MFC-MRD positive again. The remaining 174 children had completed the entire therapy. MFC-MRD was examined in 154 of them, and 153 were MFC-MRD negative. A girl with hypodiploid BCP-ALL showed a reappearance of MFC-MRD with subsequent relapse.In summary, a single 28-day course of blinatumomab immediately after induction, followed by 12 months of maintenance therapy, is highly effective in achieving MRD-negativity in children with newly diagnosed non-high risk BCP-ALL and maintaining MRD-negative remission at least during the treatment period.

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Guidelines for the use of flow cell sorting in diagnosis and monitoring of acute leukemia

Semchenkova,

Illarionova,

Demina

et al. 2023

Voprosy gematologii/onkologii i immunopatologii v pediatrii

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Flow cell sorting is an advanced laboratory technique that combines the analytical capabilities of flow cytometry with the ability to isolate pure cell populations from heterogeneous samples. It has tremendous potential both for fundamental research and laboratory diagnosis. For example, the combination of cell sorting and molecular genetic studies can be used to clarify ambiguous results of acute leukemia immunophenotyping obtained both at diagnosis and during minimal residual disease monitoring. These guidelines are based on years of experience in incorporating cell sorting into the diagnostic and monitoring processes at the Leukemia Immunophenotyping Laboratory of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. They include methods used for the confirmation of flow cytometry data depending on the type of leukemia, the stage of a flow cytometry assay and previous therapy. They also describe cell sorting algorithms for disease diagnosis and the specifics of sample preparation for cell sorting in different molecular genetic studies.

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Cytogenetic and molecular genetic diagnostics in oncohematological disorders: a position paper of the Organization of Molecular Geneticists in Oncology and Oncohematology

Cited by 7 publications

References 41 publications

Immunophenotypic but Not Genetic Changes Reclassify the Majority of Relapsed/Refractory Pediatric Cases of Early T-Cell Precursor Acute Lymphoblastic Leukemia

Immunophenotypic but Not Genetic Changes Reclassify the Majority of Relapsed/Refractory Pediatric Cases of Early T-Cell Precursor Acute Lymphoblastic Leukemia

Blinatumomab as postremission therapy replaces consolidation and substantial parts of maintenance chemotherapy and results in stable MRD negativity in children with newly diagnosed B-lineage ALL

Guidelines for the use of flow cell sorting in diagnosis and monitoring of acute leukemia

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