Abstracts Clinical Lymphoma, Myeloma & Leukemia September 2023 S344 dL/49%. This retrospective study was approved by the Ethics Committees of ANMRC in accordance with the Declaration of Helsinki. All patients signed informed consent. Patients: At the time of erythrocytosis onset median age was 46 (range, 20-55) yrs, median time of TKI treatment was 159 (range, 67–214) mos. Number of previous TKIs ranged from 0 to 4. Patients were under following TKIs: ponatinib (n=6), nilotinib (n=2) and bosutinib (n=1) with the best responses: complete hematologic response (n=2), molecular response 2 (n=2), at least major molecular response (n=5) at erythrocytosis onset. There was no history of using anabolic steroids, blood/erythropoietin (EPO) doping, or diuretics; 5/9 patients were smokers. Results: Median time from last TKI to erythrocytosis was 11 (range, 3–61) mos. At the last visit erythrocytosis was sustained in all patients except 1 who underwent stem cell transplantation. Median time of follow-up was 41 (range, 17–103) mos. All patients had a mean increase of Hgb 1.8 (range, 0.4-4.2) g/dL during TKI therapy. Median peak Hgb and Hct was 17.9 (range, 16.6–20.4) g/dL and 54.1 (range, 50.7–62.4) %, respectively. Phlebotomies were performed in 2 cases. No skin or microvascular symptoms, nor major thrombotic events were observed. All patients were negative for V617F and exon 12 JAK2 mutations. No overexpression of HIF1a or VHL were observed in 6/9 evaluable patients. All patients except one had EPO level within reference range. Testosterone levels were unremarkable in all patients. There was no evidence of EPOproducing tumors, renal artery stenosis or another renal disorders, as well as cardiac or pulmonary diseases. Conclusion: We reported erythrocytosis of unknown origin in CP-CML patients. Whether erythrocytosis might be related to TKI therapy is disputable and should be further investigated. Keywords: CML, erythrocytosis, tyrosine kinase inhibitors, case CML-480 The Clonality of Myeloid‑Derived Suppressor Cells in Chronic Myeloid Leukemia Patients Olga Kulemina MD, Tamara Chitanava MD, Roman Vlasik MD, Leonid Khordzhasov MD, Tatiana Nikulina MD, Olga Merzlikina MD, Yulia Mirolubova MD, Elena Tolstopyatova MD, Vyacheslav Solovyev MD, Nadezhda Shnalieva MD, Pavel Butylin MD, Nadezhda Luchkina MD, Alexander Ataman MD, Alexey Aronov MD, Elza Lomaia PhD Almazov National Medical Research Centre, St. Petersburg, Russian Federation Context: Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that might suppress immune responses against cancer. Recently, an accumulation of granulocytic (Gr) and monocytoid (Mo) subpopulations of MDSCs has been found in the peripheral blood of chronic phase chronic myeloid leukemia (CP-CML) patients. Are they part of the tumor clone showing BCR/ABL expression? Objective: To determine the clonality of MDSCs in CML patients. Patients: The study was approved by the Ethics Committees of Almazov National Medical Research Centre in accordance with the Declaration of Helsinki. All study patients signed informed consents. A total of 11 samples of 8 adult CP-CML patients were analyzed. Patients distributed as follow: 5 were treatment-naive for CML, 1 had a BCR::ABL level ≤1%, and 2 were without any response on tyrosine kinase inhibitors. Main Outcome Measures: Fluorescence in-situ hybridization (FISH) and PCR were performed in total MDSCs that were defined as HLADRlow/- CD11b+ CD33+. Results: Suppressive activity of MDSCs was confirmed by cocultivation with T-reg and T-cyt. BCR::ABL expression by PCR analysis was analyzed in total MDSCs samples of 6 patients (4 newly-diagnosed and 2 resistant). All samples showed a high level of BCR::ABL expression (73–110%). FISH analysis was performed in 5 samples. All samples from newly-diagnosed patients (n=3) and resistant patients (n=1) detected a high level of BCR::ABL + cells (23–100% Ph+). In one patient with optimal response, no BCR::ABL cells were revealed. Conclusions: It seems that MDSCs in CML patients arise within CML clones. Experiments to evaluate whether the sensitivity of these cells are comparable to non-MDSCs CML cells are ongoing in our centre. Keywords: CML, myeloidderived suppressor cells, chronic myeloid leukemia, clonality, FISH analysis, polymerase chain reaction BCR::ABL analysis CML-483 Mutations With Unknown Clinical Significance ‑ Another Way to Develop Resistance in Patients With CML? Daria Kustova Master1, Anna Kirienko PhD1, Ekaterina Motyko PhD1, Elizaveta Efremova MD1, Elena Morozova MD2, Vasiliy Shuvaev MD, PhD1,3, Sergey Sidorkevich MD, PhD1, Irina Martynkevich PhD1 1Russian Research Institute of Hematology and Transfusiology of the Federal Medical and Biological Agency, Saint Petersburg, Russian Federation. 2R. M. Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Saint Petersburg, Russian Federation. 3Russian Medical Academy of Postgraduate Education, Moscow, Russian Federation Context: Tyrosine kinase inhibitors (TKIs) have been successfully used to treat patients with chronic myeloid leukemia (CML). Despite the existence of several generations of inhibitors, some patients may develop resistance to TKIs. One of the causes of resistance is the presence of a mutation in the kinase domain of the BCR::ABL chimeric gene; however, BCR::ABL-independent mechanisms of resistance development are still unknown. Objective: Use nextgeneration sequencing data to evaluate the impact of mutations with unknown clinical significance on the development of resistance to TKIs. Patients: The analysis included 43 patients. The resistance group had 32 patients with resistant CML (18 men, 14 women) with a median age of 44 (IQR 14–74 years); the control group had 11 patients who responded to TKIs therapy (5 men, 6 women) with a median age of 58 (IQR 33–75 years). Cytogenetic analyses revealed additional chromosomal aberrations (ACAs) in 23% of patients in the resistant group, and in 18% of patients in the control group. Main Outcome Measures: A myeloid panel of 118 genes, with an average reading depth of 200x or 1000x on MiSeq (Illumina), was used. Clinical significance of mutations was evaluated using
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