Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2022; 21: 42-48
Низкая специфичность маркера HLA-DR для диагностики острого промиелоцитарного лейкоза
https://doi.org/10.24287/1726-1708-2022-21-1-42-48Аннотация
В основе терапии острого промиелоцитарного лейкоза (ОПЛ) лежат препараты транс-ретиноевой кислоты, эффективные только в отношении клеток с перестройками гена RARa (наиболее часто встречающаяся – t(15;17)(q24;q21)/PML::RARa). В ряде исследований авторы предлагают использовать некоторые особенности иммунофенотипа опухолевых клеток, прежде всего HLA-DRнегативность, для предсказания наличия перестройки гена RARa. Целью данной работы являлось изучение спектра генетических перестроек опухолевых клеток острого миелоидного лейкоза (ОМЛ), негативных по мембранному маркеру HLA-DR. Данное исследование одобрено независимым этическим комитетом и утверждено решением ученого совета НМИЦ ДГОИ им. Дмитрия Рогачева. Среди 806 случаев ОМЛ у детей отсутствие экспрессии HLA-DR было выявлено в 253 образцах. Из них 45,4% имели характерную для ОПЛ перестройку гена RARa (t(15;17)(q24;q21)/PML::RARa), у 54,6% она отсутствовала, при этом выявлялись другие различные генетические аномалии и хромосомные аберрации. Частота встречаемости «характерных» для ОПЛ особенностей иммунофенотипа, таких как тотальная экспрессия CD117, MPO, CD33 и отсутствие экспрессии CD34, оказалась значительно выше при наличии перестройки гена RARa, однако одновременно все данные характеристики были отмечены лишь в 66,7% случаев ОПЛ с t(15;17)(q24;q21)/PML::RARa. При этом доля позитивных клеток по маркерам CD117, CD34, MPO варьировала в широком диапазоне значений. Все исследованные «характерные» для ОПЛ особенности иммунофенотипа, такие как негативность по HLA-DR, CD34 и тотальная позитивность по CD117, CD33, MPO, а также профиль коэкспрессий лимфоидных маркеров, не являются строго специфичными для одной конкретной генетической группы ОМЛ и не могут использоваться для предсказания наличия перестройки гена RARa и постановки диагноза ОПЛ.
Список литературы
1. Grimwade D., Lo Coco F. Acute promyelocytic leukemia: a model for the role of molecular diagnosis and residual disease monitoring in directing treatment approach in acute myeloid leukemia. Leukemia 2002; 16 (10): 1959–73.
2. Zhao J., Liang J.W., Xue H.L., Shen S.H., Chen J., Tang Y.J., et al. The genetics and clinical characteristics of children morphologically diagnosed as acute promyelocytic leukemia. Leukemia 2019; 33 (6): 1387–99.
3. Wetzler M., McElwain B.K., Stewart C.C., Blumenson L., Mortazavi A., Ford L.A., et al. HLA-DR antigen-negative acute myeloid leukemia. Leukemia 2003; 17 (4): 707–15.
4. Mosleh M., Mehrpouri M., Ghaffari S., Saei Z., Agaeipoor M., Jadali F., et al. Report of a new sixpanel flow cytometry marker for early differential diagnosis of APL from HLA-DR negative Non-APL leukemia. Scand J Clin Lab Invest 2020; 80 (2): 87–92.
5. Chen Z., Li Y., Tong Y., Gao Q., Mao X., Zhang W., et al. Stepwise discriminant function analysis for rapid identification of acute promyelocytic leukemia from acute myeloid leukemia with multiparameter flow cytometry. Int J Hematol 2016; 103 (3): 306–15.
6. Bene M.C., Castoldi G., Knapp W., Ludwig W.D., Matutes E., Orfao A., et al. Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia 1995; 9 (10): 1783– 6.
7. Den Nijs J.I., Gonggrijp H.S., Augustinus E., Leeksma C.H. Hot bands: a simple G-banding method for leukemic metaphases. Cancer Genet Cytogenet 1985; 15 (3–4): 373–4.
8. Gabert J., Beillard E., van der Velden V.H., Bi W., Grimwade D., Pallisgaard N., et al. Standardization and quality control studies of 'realtime' quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia – a Europe Against Cancer program. Leukemia 2003; 17 (12): 2318–57.
9. Arber D.A., Orazi A., Hasserjian R., Thiele J., Borowitz M.J., Le Beau M.M., et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016; 127 (20): 2391–405.
10. Mendoza A.S., Qing X., Dungo M., Lasky J., Panosyan E., Cai J. HLA-DR antigen-positive acute promyelocytic leukemia. Exp Mol Pathol 2016; 101 (2): 197–200.
11. Patteet L., Vermeulen K., Pieters K., Van Assche E., Vrelust I., Gaddiseur A., et al. A hypogranular variant of acute promyelocytic leukaemia showing a heterogenic immunophenotype with CD34, CD2, HLA-DR positivity: a case report and review of the literature. Acta Clin Belg 2012; 67 (1): 34–8.
12. Devi K., Ali N. The curious case of HLA-DR-positive APL. Clin Case Rep 2021; 9 (2): 825–9.
13. Gorczyca W. Acute promyelocytic leukemia: four distinct patterns by flow cytometry immunophenotyping. Pol J Pathol 2012; 63 (1): 8–17.
Pediatric Hematology/Oncology and Immunopathology. 2022; 21: 42-48
Low specificity of HLA-DR expression for diagnosis of acute promyelocytic leukemia
https://doi.org/10.24287/1726-1708-2022-21-1-42-48Abstract
Contemporary therapy of acute promyelocytic leukemia (APL) is based on the use of all-trans retinoic acid, which is effective against tumor cells harboring RARa gene rearrangements (most common – t(15;17)(q24;q21)/PML::RARa). In several studies, it was suggested to use typical immunophenotypic features of APL (HLA-DR-negativity, etc) for prediction of RARa rearrangements presence. In this study, we aimed to evaluate the range of genetic aberrations that could be found in the HLA-DR-negative acute myeloid leukemia (AML). Our study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Among studied 806 pediatric AML patients, HLA-DR-negativity was found in 253 cases. Only in 45.4% of them t(15;17)(q24;q21)/PML::RARa was found, while in remaining 54.6% normal karyotype or other genetic aberrations without RARa involvement. Frequency of the most common immunophenotypic features of APL, such as total CD117, CD33 and MPO expression with the lack of CD34, was higher in patients with t(15;17)(q24;q21)/PML::RARa, although only two thirds of APL cases were found to have all these signs. Moreover, the percentage of cells positive or negative for mentioned antigens varied significantly in APL group. Thus we can conclude, that all “typical” immunophenotypic characteristics of APL including HLA-DR-negativity, are very unspecific and cannot be used for reliable prediction of presence of t(15;17)(q24;q21)/PML::RARa.
References
1. Grimwade D., Lo Coco F. Acute promyelocytic leukemia: a model for the role of molecular diagnosis and residual disease monitoring in directing treatment approach in acute myeloid leukemia. Leukemia 2002; 16 (10): 1959–73.
2. Zhao J., Liang J.W., Xue H.L., Shen S.H., Chen J., Tang Y.J., et al. The genetics and clinical characteristics of children morphologically diagnosed as acute promyelocytic leukemia. Leukemia 2019; 33 (6): 1387–99.
3. Wetzler M., McElwain B.K., Stewart C.C., Blumenson L., Mortazavi A., Ford L.A., et al. HLA-DR antigen-negative acute myeloid leukemia. Leukemia 2003; 17 (4): 707–15.
4. Mosleh M., Mehrpouri M., Ghaffari S., Saei Z., Agaeipoor M., Jadali F., et al. Report of a new sixpanel flow cytometry marker for early differential diagnosis of APL from HLA-DR negative Non-APL leukemia. Scand J Clin Lab Invest 2020; 80 (2): 87–92.
5. Chen Z., Li Y., Tong Y., Gao Q., Mao X., Zhang W., et al. Stepwise discriminant function analysis for rapid identification of acute promyelocytic leukemia from acute myeloid leukemia with multiparameter flow cytometry. Int J Hematol 2016; 103 (3): 306–15.
6. Bene M.C., Castoldi G., Knapp W., Ludwig W.D., Matutes E., Orfao A., et al. Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia 1995; 9 (10): 1783– 6.
7. Den Nijs J.I., Gonggrijp H.S., Augustinus E., Leeksma C.H. Hot bands: a simple G-banding method for leukemic metaphases. Cancer Genet Cytogenet 1985; 15 (3–4): 373–4.
8. Gabert J., Beillard E., van der Velden V.H., Bi W., Grimwade D., Pallisgaard N., et al. Standardization and quality control studies of 'realtime' quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia – a Europe Against Cancer program. Leukemia 2003; 17 (12): 2318–57.
9. Arber D.A., Orazi A., Hasserjian R., Thiele J., Borowitz M.J., Le Beau M.M., et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016; 127 (20): 2391–405.
10. Mendoza A.S., Qing X., Dungo M., Lasky J., Panosyan E., Cai J. HLA-DR antigen-positive acute promyelocytic leukemia. Exp Mol Pathol 2016; 101 (2): 197–200.
11. Patteet L., Vermeulen K., Pieters K., Van Assche E., Vrelust I., Gaddiseur A., et al. A hypogranular variant of acute promyelocytic leukaemia showing a heterogenic immunophenotype with CD34, CD2, HLA-DR positivity: a case report and review of the literature. Acta Clin Belg 2012; 67 (1): 34–8.
12. Devi K., Ali N. The curious case of HLA-DR-positive APL. Clin Case Rep 2021; 9 (2): 825–9.
13. Gorczyca W. Acute promyelocytic leukemia: four distinct patterns by flow cytometry immunophenotyping. Pol J Pathol 2012; 63 (1): 8–17.
