Skip to main content
Erschienen in:

16.09.2023 | REVIEW ARTICLE

Analytical Appraisal of Hematogones in B-ALL MRD Assessment Using Multidimensional Dot-Plots by Multiparametric Flow Cytometry: A Critical Review and Update

verfasst von: Nupur Das, Smeeta Gajendra, Ritu Gupta

Erschienen in: Indian Journal of Hematology and Blood Transfusion | Ausgabe 1/2024

Einloggen, um Zugang zu erhalten

Abstract

The spectrum of benign B-cell precursors, known as hematogones (HGs), shows a significant morphological and immunophenotypic overlap with their malignant counterpart i.e. B-lymphoid blasts (BLBs). This results in a diagnostic dilemma in assessment of cases wherein there is a physiological preponderance of HGs and also poses a significant challenge in measurable residual disease assessment in B-cell acute lymphoblastic leukaemia. Consequently, expression patterns of various immunophenotypic markers are considered the most important tool in identification and delineation of HGs from BLBs. However, certain aspects of B-cell compartment evaluation by flow cytometric immunophenotyping and its relevance in clinical scenarios is yet to be defined precisely. This review summarizes current flowcytometric data on HGs and its discrimination from BLBs based on thorough review of literature and evaluation of in-house data. Furthermore, it focuses on the utility of an additional analytical tool i.e., radar plot for a comprehensive representation of various subsets of the B-cell compartment and their differentiation from BLBs.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Rimsza LM, Larson RS, Winter SS et al (2000) Benign hematogone-rich lymphoid proliferations can be distinguished from B-lineage acute lymphoblastic leukemia by integration of morphology, immunophenotype, adhesion molecule expression, and architectural features. Am J Clin Pathol 114(1):66–75. https://doi.org/10.1309/LXU4-Q7Q9-3YAB-4QE0CrossRefPubMed Rimsza LM, Larson RS, Winter SS et al (2000) Benign hematogone-rich lymphoid proliferations can be distinguished from B-lineage acute lymphoblastic leukemia by integration of morphology, immunophenotype, adhesion molecule expression, and architectural features. Am J Clin Pathol 114(1):66–75. https://​doi.​org/​10.​1309/​LXU4-Q7Q9-3YAB-4QE0CrossRefPubMed
8.
Zurück zum Zitat Lúcio P, Parreira A, van den Beemd MW, van Lochem EG, van Wering ER, Baars E, Porwit-MacDonald A, Bjorklund E, Gaipa G, Biondi A, Orfao A, Janossy G, van Dongen JJ, San Miguel JF (1999) Flow cytometric analysis of normal B cell differentiation: a frame of reference for the detection of minimal residual disease in precursor-B-ALL. Leukemia 13(3):419–427. https://doi.org/10.1038/sj.leu.2401279CrossRefPubMed Lúcio P, Parreira A, van den Beemd MW, van Lochem EG, van Wering ER, Baars E, Porwit-MacDonald A, Bjorklund E, Gaipa G, Biondi A, Orfao A, Janossy G, van Dongen JJ, San Miguel JF (1999) Flow cytometric analysis of normal B cell differentiation: a frame of reference for the detection of minimal residual disease in precursor-B-ALL. Leukemia 13(3):419–427. https://​doi.​org/​10.​1038/​sj.​leu.​2401279CrossRefPubMed
10.
Zurück zum Zitat Theunissen PMJ, Sedek L, De Haas V, Szczepanski T, Van Der Sluijs A, Mejstrikova E, Nováková M, Kalina T, Lecrevisse Q, Orfao A, Lankester AC, van Dongen JJM, Van Der Velden VHJ, EuroFlow Consortium (2017) Detailed immunophenotyping of B-cell precursors in regenerating bone marrow of acute lymphoblastic leukaemia patients: implications for minimal residual disease detection. Br J Haematol 178(2):257–266. https://doi.org/10.1111/bjh.14682CrossRefPubMed Theunissen PMJ, Sedek L, De Haas V, Szczepanski T, Van Der Sluijs A, Mejstrikova E, Nováková M, Kalina T, Lecrevisse Q, Orfao A, Lankester AC, van Dongen JJM, Van Der Velden VHJ, EuroFlow Consortium (2017) Detailed immunophenotyping of B-cell precursors in regenerating bone marrow of acute lymphoblastic leukaemia patients: implications for minimal residual disease detection. Br J Haematol 178(2):257–266. https://​doi.​org/​10.​1111/​bjh.​14682CrossRefPubMed
11.
Zurück zum Zitat Das N, Gupta R, Gupta SK, Bakhshi S, Seth R, Kumar C, Rai S, Singh S, Prajapati VK, Gogia A, Sahoo RK, Sharma A, Kumar L (2021) Critical evaluation of the utility of pre- and post-therapy immunophenotypes in assessment of measurable residual disease in B-ALL. Ann Hematol 100(10):2487–2500. https://doi.org/10.1007/s00277-021-04580-2CrossRefPubMed Das N, Gupta R, Gupta SK, Bakhshi S, Seth R, Kumar C, Rai S, Singh S, Prajapati VK, Gogia A, Sahoo RK, Sharma A, Kumar L (2021) Critical evaluation of the utility of pre- and post-therapy immunophenotypes in assessment of measurable residual disease in B-ALL. Ann Hematol 100(10):2487–2500. https://​doi.​org/​10.​1007/​s00277-021-04580-2CrossRefPubMed
13.
Zurück zum Zitat Chatterjee G, Sriram H, Ghogale S, Deshpande N, Khanka T, Panda D, Pradhan SN, Girase K, Narula G, Dhamane C, Malik NR, Banavali S, Patkar NV, Gujral S, Subramanian PG, Tembhare PR (2021) Immunophenotypic shift in the B-cell precursors from regenerating bone marrow samples: a critical consideration for measurable residual disease assessment in B-lymphoblastic leukemia. Cytometry B Clin Cytom 100(4):434–445. https://doi.org/10.1002/cyto.b.21951CrossRefPubMed Chatterjee G, Sriram H, Ghogale S, Deshpande N, Khanka T, Panda D, Pradhan SN, Girase K, Narula G, Dhamane C, Malik NR, Banavali S, Patkar NV, Gujral S, Subramanian PG, Tembhare PR (2021) Immunophenotypic shift in the B-cell precursors from regenerating bone marrow samples: a critical consideration for measurable residual disease assessment in B-lymphoblastic leukemia. Cytometry B Clin Cytom 100(4):434–445. https://​doi.​org/​10.​1002/​cyto.​b.​21951CrossRefPubMed
16.
Zurück zum Zitat Ishio T, Sugita J, Tateno T, Hidaka D, Hayase E, Shiratori S, Okada K, Goto H, Onozawa M, Nakagawa M, Hashimoto D, Kahata K, Fujimoto K, Endo T, Kondo T, Teshima T (2018) Hematogones predict better outcome in allogeneic hematopoietic stem cell transplantation irrespective of graft sources. Biol Blood Marrow Transplant 24(10):1990–1996. https://doi.org/10.1016/j.bbmt.2018.06.011CrossRefPubMed Ishio T, Sugita J, Tateno T, Hidaka D, Hayase E, Shiratori S, Okada K, Goto H, Onozawa M, Nakagawa M, Hashimoto D, Kahata K, Fujimoto K, Endo T, Kondo T, Teshima T (2018) Hematogones predict better outcome in allogeneic hematopoietic stem cell transplantation irrespective of graft sources. Biol Blood Marrow Transplant 24(10):1990–1996. https://​doi.​org/​10.​1016/​j.​bbmt.​2018.​06.​011CrossRefPubMed
23.
Zurück zum Zitat Theunissen P, Mejstrikova E, Sedek L, van der Sluijs-Gelling AJ, Gaipa G, Bartels M, Sobral da Costa E, Kotrová M, Novakova M, Sonneveld E, Buracchi C, Bonaccorso P, Oliveira E, Te Marvelde JG, Szczepanski T, Lhermitte L, Hrusak O, Lecrevisse Q, Grigore GE, Froňková E, Trka J, Brüggemann M, Orfao A, van Dongen JJ, van der Velden VH, EuroFlow Consortium (2017) Standardized flow cytometry for highly sensitive MRD measurements in B-cell acute lymphoblastic leukemia. Blood 129(3):347–357. https://doi.org/10.1182/blood-2016-07-726307CrossRefPubMedPubMedCentral Theunissen P, Mejstrikova E, Sedek L, van der Sluijs-Gelling AJ, Gaipa G, Bartels M, Sobral da Costa E, Kotrová M, Novakova M, Sonneveld E, Buracchi C, Bonaccorso P, Oliveira E, Te Marvelde JG, Szczepanski T, Lhermitte L, Hrusak O, Lecrevisse Q, Grigore GE, Froňková E, Trka J, Brüggemann M, Orfao A, van Dongen JJ, van der Velden VH, EuroFlow Consortium (2017) Standardized flow cytometry for highly sensitive MRD measurements in B-cell acute lymphoblastic leukemia. Blood 129(3):347–357. https://​doi.​org/​10.​1182/​blood-2016-07-726307CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Tembhare PR, Ghogale S, Ghatwai N, Badrinath Y, Kunder N, Patkar NV, Bibi AR, Chatterjee G, Arora B, Narula G, Banawali S, Deshpande N, Amare P, Gujral S, Subramanian PG (2018) Evaluation of new markers for minimal residual disease monitoring in B-cell precursor acute lymphoblastic leukemia: CD73 and CD86 are the most relevant new markers to increase the efficacy of MRD. Cytom B Clin Cytom 94(1):100–111. https://doi.org/10.1002/cyto.b.21486CrossRef Tembhare PR, Ghogale S, Ghatwai N, Badrinath Y, Kunder N, Patkar NV, Bibi AR, Chatterjee G, Arora B, Narula G, Banawali S, Deshpande N, Amare P, Gujral S, Subramanian PG (2018) Evaluation of new markers for minimal residual disease monitoring in B-cell precursor acute lymphoblastic leukemia: CD73 and CD86 are the most relevant new markers to increase the efficacy of MRD. Cytom B Clin Cytom 94(1):100–111. https://​doi.​org/​10.​1002/​cyto.​b.​21486CrossRef
26.
Zurück zum Zitat Mikhailova E, Semchenkova A, Illarionova O, Kashpor S, Brilliantova V, Zakharova E, Zerkalenkova E, Zangrando A, Bocharova N, Shelikhova L, Diakonova Y, Zhogov V, Khismatullina R, Molostova O, Buldini B, Raykina E, Larin S, Olshanskaya Y, Miakova N, Novichkova G, Maschan M, Popov AM (2021) Relative expansion of CD19-negative very-early normal B-cell precursors in children with acute lymphoblastic leukaemia after CD19 targeting by blinatumomab and CAR-T cell therapy: implications for flow cytometric detection of minimal residual disease. Br J Haematol 193(3):602–612. https://doi.org/10.1111/bjh.17382CrossRefPubMed Mikhailova E, Semchenkova A, Illarionova O, Kashpor S, Brilliantova V, Zakharova E, Zerkalenkova E, Zangrando A, Bocharova N, Shelikhova L, Diakonova Y, Zhogov V, Khismatullina R, Molostova O, Buldini B, Raykina E, Larin S, Olshanskaya Y, Miakova N, Novichkova G, Maschan M, Popov AM (2021) Relative expansion of CD19-negative very-early normal B-cell precursors in children with acute lymphoblastic leukaemia after CD19 targeting by blinatumomab and CAR-T cell therapy: implications for flow cytometric detection of minimal residual disease. Br J Haematol 193(3):602–612. https://​doi.​org/​10.​1111/​bjh.​17382CrossRefPubMed
28.
32.
Zurück zum Zitat Sherif LM, Azab MM, Al-Akad GM, Zakaria M, Atfy M, Sorour SM (2017) Cluster of differentiation 97 as a biomarker for the detection of minimal residual disease in common acute lymphoblastic leukemia. Egypt J Haematol 42:81–87CrossRef Sherif LM, Azab MM, Al-Akad GM, Zakaria M, Atfy M, Sorour SM (2017) Cluster of differentiation 97 as a biomarker for the detection of minimal residual disease in common acute lymphoblastic leukemia. Egypt J Haematol 42:81–87CrossRef
42.
Zurück zum Zitat Costa ES, Pedreira CE, Barrena S, Lecrevisse Q, Flores J, Quijano S, Almeida J, del Carmen G-M, Bottcher S, Van Dongen JJ, Orfao A (2011) Automated pattern-guided principal component analysis vs expert-based immunophenotypic classification of B-cell chronic lymphoproliferative disorders: a step forward in the standardization of clinical immunophenotyping. Leukemia 25(2):385. https://doi.org/10.1038/leu.2010.160CrossRefPubMedCentral Costa ES, Pedreira CE, Barrena S, Lecrevisse Q, Flores J, Quijano S, Almeida J, del Carmen G-M, Bottcher S, Van Dongen JJ, Orfao A (2011) Automated pattern-guided principal component analysis vs expert-based immunophenotypic classification of B-cell chronic lymphoproliferative disorders: a step forward in the standardization of clinical immunophenotyping. Leukemia 25(2):385. https://​doi.​org/​10.​1038/​leu.​2010.​160CrossRefPubMedCentral
44.
Zurück zum Zitat Amirel AD, Davis KL, Tadmor MD, Simonds EF, Levine JH, Bendall SC, Shenfeld DK, Krishnaswamy S, Nolan GP, Pe’er D (2013) viSNE enables visualization of high dimensional single-cell data and reveals phenotypic heterogeneity of leukemia. Nat Biotechnol 31(6):545–552. https://doi.org/10.1038/nbt.2594CrossRef Amirel AD, Davis KL, Tadmor MD, Simonds EF, Levine JH, Bendall SC, Shenfeld DK, Krishnaswamy S, Nolan GP, Pe’er D (2013) viSNE enables visualization of high dimensional single-cell data and reveals phenotypic heterogeneity of leukemia. Nat Biotechnol 31(6):545–552. https://​doi.​org/​10.​1038/​nbt.​2594CrossRef
46.
Zurück zum Zitat Reiter M, Diem M, Schumich A, Maurer-Granofszky M, Karawajew L, Rossi JG, Ratei R, Groeneveld-Krentz S, Sajaroff EO, Suhendra S, Kampel M, Dworzak MN, International Berlin-Frankfurt-Münster (iBFM)-FLOW-network and the AutoFLOW consortium (2019) Automated flow cytometric MRD assessment in childhood acute B-lymphoblastic leukemia using supervised machine learning. Cytometry A 95(9):966–975. https://doi.org/10.1002/cyto.a.23852CrossRefPubMed Reiter M, Diem M, Schumich A, Maurer-Granofszky M, Karawajew L, Rossi JG, Ratei R, Groeneveld-Krentz S, Sajaroff EO, Suhendra S, Kampel M, Dworzak MN, International Berlin-Frankfurt-Münster (iBFM)-FLOW-network and the AutoFLOW consortium (2019) Automated flow cytometric MRD assessment in childhood acute B-lymphoblastic leukemia using supervised machine learning. Cytometry A 95(9):966–975. https://​doi.​org/​10.​1002/​cyto.​a.​23852CrossRefPubMed
48.
Zurück zum Zitat Gupta M, Jafari K, Rajab A, Wei C, Mazur J, Tierens A, Hyjek E, Musani R, Porwit A (2021) Radar plots facilitate differential diagnosis of acute promyelocytic leukemia and NPM1+ acute myeloid leukemia by flow cytometry. Cytom B Clin Cytom 100(4):409–420. https://doi.org/10.1002/cyto.b.21979CrossRef Gupta M, Jafari K, Rajab A, Wei C, Mazur J, Tierens A, Hyjek E, Musani R, Porwit A (2021) Radar plots facilitate differential diagnosis of acute promyelocytic leukemia and NPM1+ acute myeloid leukemia by flow cytometry. Cytom B Clin Cytom 100(4):409–420. https://​doi.​org/​10.​1002/​cyto.​b.​21979CrossRef
51.
Zurück zum Zitat Kárai B, Tisza K, Eperjesi O, Nagy AC, Ujfalusi A, Kelemen Á, Szegedi I, Kiss C, Kappelmayer J, Hevessy Z (2021) A novel method for the evaluation of bone marrow samples from patients with pediatric B-cell acute lymphoblastic leukemia-multidimensional flow cytometry. Cancers (Basel) 13(20):5044. https://doi.org/10.3390/cancers13205044CrossRefPubMed Kárai B, Tisza K, Eperjesi O, Nagy AC, Ujfalusi A, Kelemen Á, Szegedi I, Kiss C, Kappelmayer J, Hevessy Z (2021) A novel method for the evaluation of bone marrow samples from patients with pediatric B-cell acute lymphoblastic leukemia-multidimensional flow cytometry. Cancers (Basel) 13(20):5044. https://​doi.​org/​10.​3390/​cancers13205044CrossRefPubMed
52.
Zurück zum Zitat Violidaki D, Axler O, Jafari K, Bild F, Nilsson L, Mazur J, Ehinger M, Porwit A (2020) Analysis of erythroid maturation in the nonlysed bone marrow with help of radar plots facilitates detection of flow cytometric aberrations in myelodysplastic syndromes. Cytom B Clin Cytom 98(5):399–411. https://doi.org/10.1002/cyto.b.21931CrossRef Violidaki D, Axler O, Jafari K, Bild F, Nilsson L, Mazur J, Ehinger M, Porwit A (2020) Analysis of erythroid maturation in the nonlysed bone marrow with help of radar plots facilitates detection of flow cytometric aberrations in myelodysplastic syndromes. Cytom B Clin Cytom 98(5):399–411. https://​doi.​org/​10.​1002/​cyto.​b.​21931CrossRef
53.
Metadaten
Titel
Analytical Appraisal of Hematogones in B-ALL MRD Assessment Using Multidimensional Dot-Plots by Multiparametric Flow Cytometry: A Critical Review and Update
verfasst von
Nupur Das
Smeeta Gajendra
Ritu Gupta
Publikationsdatum
16.09.2023
Verlag
Springer India
Erschienen in
Indian Journal of Hematology and Blood Transfusion / Ausgabe 1/2024
Print ISSN: 0971-4502
Elektronische ISSN: 0974-0449
DOI
https://doi.org/10.1007/s12288-023-01696-5

Neu im Fachgebiet Onkologie

Frühe CLL-Therapie: BTK-Hemmer verlängert EFS und PFS, aber nicht OS

Auch nach sechs Jahren ergibt sich kein Überlebensvorteil einer Therapie mit dem BTK-Hemmer Ibrutinib für Menschen mit frühem CLL-Stadium und erhöhtem Progressionsrisiko. Die Progressionsrate wird mit der Behandlung jedoch um über 80% gesenkt.

Adjuvantes Atezolizumab ohne Nutzen bei frühem TNBC

Patientinnen mit frühem triple-negativem Brustkrebs profitieren nach der Operation offenbar nicht von einer Zugabe des PD-L1-Hemmers Atezolizumab zur adjuvanten Standardchemotherapie. Die Studie, die das untersucht hat, wurde vorzeitig abgebrochen. Was könnte die schlechte Wirksamkeit erklären?

Brustkrebstherapie: zu wenig Aufklärung über Nebenwirkungen?

Ergebnisse eines internationalen Surveys legen nahe, dass die Aufklärung über Nebenwirkungen einer Brustkrebstherapie häufig unzureichend ausfällt bzw. zu spät erfolgt.

Neue chemotherapiefreie Kombinationstherapie punktet bei CLL

Zwischenergebnisse der Phase-III-Studie AMPLIFY sprechen dafür, dass die zeitlich begrenzte Behandlung mit Acalabrutinib und Venetoclax fitte Personen mit chronischer lymphatischer Leukämie länger leben lässt als eine Chemoimmuntherapie.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.