Detection and monitoring of minimal residual disease in acute megakaryoblastic leukemia in children
- Authors: Palladina A.D.1, Popa A.V.2, Valiev T.T.1, Nikitaev V.G.3, Chernysheva O.A.1, Kupryshina N.A.1, Serebryakova I.N.1, Shvedova T.V.1, Kondratchik K.L.2,4, Tupitsyn N.N.1
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Affiliations:
- Blokhin National Medical Research Center of Oncology
- Pirogov Russian National Research Medical University
- National Research Nuclear University MEPhI
- Morozov Children’s Clinical Hospital
- Issue: Vol 23, No 1 (2021)
- Pages: 148-155
- Section: CLINICAL ONCOLOGY
- URL: https://journals.rcsi.science/1815-1434/article/view/70472
- DOI: https://doi.org/10.26442/18151434.2021.1.200762
- ID: 70472
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Abstract
Acute megakaryoblastic leukemia (AMKL) is a rare subtype of acute myeloid leukemia (AML), which is associated with poor prognosis for all patients except children with t(1;22) or Down syndrome. The frequency of complete remission in case of AMKL is comparable to the frequency of complete remission in other variants of AML, and the median survival is much lower. This determines the necessity to update criteria for assessment of the effect of treatment using flow cytometry definition of the level of minimal residual disease (MRD). Nowadays, there are no unified and standardized approaches for the measurement of MRD in case of myeloid leukemia, including AMKL, which prohibits adequate assessment of the therapy effect and in some cases – determination of the indications for allogeneic hematopoietic stem cells transplantation. The article identifies diagnostic features and describes approaches for the measurement of the level of MRD in case of AMKL.
Aim. The aim is to demonstrate the algorithms for diagnosing and measuring MRD in case of AML-M7 in children.
Materials and methods. The article analyzes the clinical and immunological profile of 10 boys and 4 girls with the initial diagnosis of AMKL between the ages of 3 months – 12 years old, 13 of them have received treatment in the FSBI «N.N. Blokhin National Medical Research Center of Oncology» and one – in the GBUZ «Morozovsky DGKB» between 1995 and 2020, The measurement of MRD was carried out in 6 patients. The measurement of MRD was carried out using both morphocytochemical method and multiparameter flow cytometry with megakaryocyte markers (CD61, CD42, CD41) in combination with other myeloid markers (CD13, CD33), CD34, CD117 and aberrant markers (mainly CD7).
Results. We showed that adequate measurement of the level of MRD had required detailed immunophenotyping during diagnosis to determine the aberration of megakaryoblasts. CD9 marker (100%), CD33 myeloid marker (69.2%), stem cell antigen CD34 (46.2%), CD13 (38.2%) in addition to megakaryocyte markers (100%) were most often expressed on blast cells in case of AMKL. The CD117 antigen was present on the blasts in 33.3% of cases. The expression of the T-cell-associated CD7 antigen (46.2%) was frequent. The measurement of MRD was carried out during the treatment (usually after an induction course) on the basis of the markers of megakaryocytic cell line (CD61, CD41, CD42a, CD42b), weak CD45 expression, as well as the immunophenotype characteristics during initial diagnosis. The level of MRD ranged from completely negative (0%; 0.006%) to evident (1.05%).
Conclusion. The detection of residual tumor megakaryoblasts in case of AML-M7 using flow cytometry is a promising method to evaluate the effect of therapy. The adequate measurement of the level of MRD requires detailed immunophenotyping during the diagnosis to determine the aberration of megakaryoblasts.
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##article.viewOnOriginalSite##About the authors
Alexandra D. Palladina
Blokhin National Medical Research Center of Oncology
Author for correspondence.
Email: palladinaa@gmail.com
ORCID iD: 0000-0002-9400-7347
doctor, Blokhin National Medical Research Center of Oncology
Russian Federation, MoscowAleksandr V. Popa
Pirogov Russian National Research Medical University
Email: apopa@list.ru
ORCID iD: 0000-0001-5318-8033
D. Sci. (Med.), Prof. RAS
Russian Federation, MoscowTimur T. Valiev
Blokhin National Medical Research Center of Oncology
Email: timurvaliev@mail.ru
ORCID iD: 0000-0002-1469-2365
D. Sci. (Med.)
Russian Federation, MoscowValentin G. Nikitaev
National Research Nuclear University MEPhI
Email: kaf46@mail.ru
ORCID iD: 0000-0002-4349-3023
D. Sci. (Techn.)
Russian Federation, MoscowOlga A. Chernysheva
Blokhin National Medical Research Center of Oncology
Email: beznos.olga@gmail.com
ORCID iD: 0000-0002-9630-5591
Cand. Sci. (Med.)
Russian Federation, MoscowNatalia A. Kupryshina
Blokhin National Medical Research Center of Oncology
Email: 2511@yandex.ru
ORCID iD: 0000-0001-8509-0954
Cand. Sci. (Med.)
Russian Federation, MoscowIrina N. Serebryakova
Blokhin National Medical Research Center of Oncology
Email: palladinaa@gmail.com
ORCID iD: 0000-0002-8389-4737
Cand. Sci. (Med.)
Russian Federation, MoscowTamara V. Shvedova
Blokhin National Medical Research Center of Oncology
Email: palladinaa@gmail.com
biologist
Russian Federation, MoscowKonstantin L. Kondratchik
Pirogov Russian National Research Medical University; Morozov Children’s Clinical Hospital
Email: morozov-14@yandex.ru
ORCID iD: 0000-0002-5195-4539
Cand. Sci. (Med.)
Russian Federation, Moscow; MoscowNikolai N. Tupitsyn
Blokhin National Medical Research Center of Oncology
Email: nntca@yahoo.com
ORCID iD: 0000-0003-3966-128X
D. Sci. (Med.)
Russian Federation, MoscowReferences
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