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Chapter 22 : Acute Myeloid Leukemia: Diagnosis and Minimal Residual Disease Detection by Flow Cytometry

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Acute Myeloid Leukemia: Diagnosis and Minimal Residual Disease Detection by Flow Cytometry, Page 1 of 2

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Abstract:

Flow cytometry is an integral tool in both the diagnosis and posttherapy evaluation of acute myeloid leukemia (AML). The strength of the technology is its capacity for rapid, sequential single-cell analysis with simultaneous evaluation of multiple antigens, thus providing a comprehensive immunophenotype for discrete cellular subpopulations. As a result, it has become the methodology of choice for determining blast lineage and immunophenotype. Cytochemical or immunohistochemical evaluation, although useful and even required in some settings, has been surpassed by flow cytometry for the evaluation of blood and marrow in most instances (1, 2). Nevertheless, flow cytometric findings must be used in conjunction with morphology, molecular, and cytogenetic findings for the complete diagnosis and subclassification of AML. Evaluation of posttherapy samples for residual acute myeloid leukemia allows enumeration of blasts as low as 1% by morphology; however, distinguishing normal or regenerating progenitors from leukemic blasts rarely can be performed by morphologic examination alone. Flow cytometry not only allows a more sensitive assay, in some cases reaching a sensitivity of 0.01% (3–5), it is also able to identify aberrancies on the leukemic blast population that allow discrimination from normal or regenerating progenitors (2, 6, 7). These attributes make flow cytometry an ideal method for evaluating for minimal residual disease (MRD) in the posttherapy setting.

Citation: Wood B, Soma L. 2016. Acute Myeloid Leukemia: Diagnosis and Minimal Residual Disease Detection by Flow Cytometry, p 217-225. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch22
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Figures

Image of FIGURE 1
FIGURE 1

Example dot plots of normal, early stem cells (purple) and normal CD34-positive blasts (red). Upper left dot plot shows CD45 versus side scatter (blue: lymphocytes; pink: monocytes; green: maturing granulocytes; aqua: hematogones) with circled area defining the blast region. Remaining dot plots are selectively displaying CD34-positive progenitors only. Myeloid progenitors show increasing expression of CD13, CD33, CD117, and HLA-DR.

Citation: Wood B, Soma L. 2016. Acute Myeloid Leukemia: Diagnosis and Minimal Residual Disease Detection by Flow Cytometry, p 217-225. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch22
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Image of FIGURE 2
FIGURE 2

Example dot plots of acute myeloid leukemia (red). Upper left dot plot shows CD45 versus side scatter with blast population highlighted in red. Remaining dot plots are selectively displaying CD34-positive leukemic blasts only. Notice, compared to normal myeloid blasts in Fig. 1 , these abnormal, leukemic blasts demonstrate lower side scatter, variably increased CD13, early/abnormal expression of CD15, decreased to absent CD33, variably increased CD34, variably decreased CD45, variably increased CD117, and variably decreased HLA-DR.

Citation: Wood B, Soma L. 2016. Acute Myeloid Leukemia: Diagnosis and Minimal Residual Disease Detection by Flow Cytometry, p 217-225. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch22
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Image of FIGURE 3
FIGURE 3

Example dot plots of minimal residual disease (MRD; purple population visualized on CD34 gating) with associated regenerating normal myeloid blasts (red). Upper left dot plot shows CD45 versus side scatter (blue, lymphocytes; pink, monocytes; green, maturing granulocytes; aqua, hematogones) with circled area defining the blast region. Remaining dot plots are selectively displaying emphasized, CD34-positive progenitors only. The MRD-positive population (purple) shows abnormal expression of CD4, decreased to absent CD13, uniform CD33, increased CD34, absent CD38, increased CD45, and subset CD56 (not shown) with normal expression of CD117 and HLA-DR and normal lack of CD15. Although the total CD34-positive population accounted for 2% of the white cells, the abnormal, MRD-positive population accounted for 0.03% of the white cells.

Citation: Wood B, Soma L. 2016. Acute Myeloid Leukemia: Diagnosis and Minimal Residual Disease Detection by Flow Cytometry, p 217-225. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch22
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References

/content/book/10.1128/9781555818722.ch22
1. Craig FE, Foon KA. 2008. Flow cytometric immunophenotyping for hematologic neoplasms Blood 111:39413967.[CrossRef].[PubMed]
2. Wood BL. 2007. Myeloid malignancies: myelodysplastic syndromes, myeloproliferative disorders, and acute myeloid leukemia Clin Lab Med 27:551575.[CrossRef].[PubMed]
3. Coustan-Smith E, Ribeiro RC, Rubnitz JE, Razzouk BI, Pui CH, Pounds S, Andreansky M, Behm FG, Raimondi SC, Shurtleff SA, Downing JR, Campana D. 2003. Clinical significance of residual disease during treatment in childhood acute myeloid leukaemia Br J Haematol 123:243252.[PubMed].[CrossRef]
4. San Miguel JF, Vidriales MB, Lopez-Berges C, Diaz-Mediavilla J, Gutierrez N, Canizo C, Ramos F, Calmuntia MJ, Perez JJ, Gonzalez M, Orfao A. 2001. Early immunophenotypical evaluation of minimal residual disease in acute myeloid leukemia identifies different patient risk groups and may contribute to postinduction treatment stratification Blood 98:17461751.[PubMed].[CrossRef]
5. Venditti A, Buccisano F, Del Poeta G, Maurillo L, Tamburini A, Cox C, Battaglia A, Catalano G, Del Moro B, Cudillo L, Postorino M, Masi M, Amadori S. 2000. Level of minimal residual disease after consolidation therapy predicts outcome in acute myeloid leukemia Blood 96:39483952.[PubMed]
6. Al-Mawali A, Gillis D, Lewis I. 2009. The role of multiparameter flow cytometry for detection of minimal residual disease in acute myeloid leukemia Am J Clin Pathol 131:1626.[CrossRef].[PubMed]
7. Soma L, Wood BL. 2013. Minimal residual disease testing in acute leukemia Int J Hematol Oncol 216:467485.[CrossRef]
8. Arnoulet C, Bene MC, Durrieu F, Feuillard J, Fossat C, Husson B, Jouault H, Maynadie M, Lacombe F. 2010. Four- and five-color flow cytometry analysis of leukocyte differentiation pathways in normal bone marrow: a reference document based on a systematic approach by the GTLLF and GEIL Cytometry B Clin Cytom 78:410.[CrossRef].[PubMed]
9. Gorczyca W, Sun ZY, Cronin W, Li X, Mau S, Tugulea S. 2011. Immunophenotypic pattern of myeloid populations by flow cytometry analysis Methods Cell Biol 103:221266.
10. Wood B. 2004. Multicolor immunophenotyping: human immune system hematopoiesis Methods Cell Biol 75:559576.[PubMed].[CrossRef]
11. Garg S, Madkaikar M, Ghosh K. 2013. Investigating cell surface markers on normal hematopoietic stem cells in three different niche conditions Int J Stem Cells 6:129133.[PubMed].[CrossRef]
12. Manz MG, Miyamoto T, Akashi K, Weissman IL. 2002. Prospective isolation of human clonogenic common myeloid progenitors Proc Natl Acad Sci USA 99:1187211877.[CrossRef].[PubMed]
13. Ratajczak MZ. 2008. Phenotypic and functional characterization of hematopoietic stem cells Curr Opin Hematol 15:293300.[CrossRef].[PubMed]
14. Kussick SJ, Wood BL. 2003. Using 4-color flow cytometry to identify abnormal myeloid populations Arch Pathol Lab Med 127:11401147.[CrossRef].[PubMed]
15. van Lochem EG, van der Velden VH, Wind HK, te Marvelde JG, Westerdaal NA, van Dongen JJ. 2004. Immunophenotypic differentiation patterns of normal hematopoiesis in human bone marrow: reference patterns for age-related changes and disease-induced shifts Cytometry B Clin Cytom 60:113.[CrossRef].[PubMed]
16. Loken MR, Shah VO, Dattilio KL, Civin CI. 1987. Flow cytometric analysis of human bone marrow: I. Normal erythroid development. Blood 69:255263.[PubMed]
17. Tomer A, Harker LA, Burstein SA. 1988. Flow cytometric analysis of normal human megakaryocytes Blood 71:12441252.[PubMed]
18. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW. 2008. World Health Organization Classification of Tumors of Hematopoietic and Lymphoid Tissues. IARC Press, Lyon, France.
19. Deschler B, Lubbert M. 2006. Acute myeloid leukemia: epidemiology and etiology Cancer 107:209920107.[CrossRef].[PubMed]
20. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, Sultan C. 1976. Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group Br J Haematol 33:451458.[PubMed].[CrossRef]
21. Jaffe ES, Harris NL, Stein H, Vardiman J. 2001. World Health Organization Classification of Tumors: Pathology and Genetics of Tumours of Hematopoietic and Lymphoid Tissues. IARC Press, Lyon, France.
22. Cherian S, Wood BL. 2012. Flow Cytometry in Evaluation of Hematopoietic Neoplasms: A Case-based Approach. CAP Press, Northfield, IL.
23. Lo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Iacobelli S, Ferrara F, Fazi P, Cicconi L, Di Bona E, Specchia G, Sica S, Divona M, Levis A, Fiedler W, Cerqui E, Breccia M, Fioritoni G, Salih HR, Cazzola M, Melillo L, Carella AM, Brandts CH, Morra E, von Lilienfeld-Toal M, Hertenstein B, Wattad M, Lubbert M, Hanel M, Schmitz N, Link H, Kropp MG, Rambaldi A, La Nasa G, Luppi M, Ciceri F, Finizio O, Venditti A, Fabbiano F, Dohner K, Sauer M, Ganser A, Amadori S, Mandelli F, Dohner H, Ehninger G, Schlenk RF, Platzbecker U Gruppo Italiano Malattie Ematologiche dell'Adulto; German-Austrian Acute Myeloid Leukemia Study Group; Study Alliance Leukemia. 2013. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia N Engl J Med 369:111121.[CrossRef].[PubMed]
24. Lallemand-Breitenbach V, de Thé H. 2013. Retinoic acid plus arsenic trioxide, the ultimate panacea for acute promyelocytic leukemia? Blood 122:20082010.[CrossRef].[PubMed]
25. Stelzer GT, Marti G, Hurley A, McCoy P Jr, Lovett EJ, Schwartz A. 1997. U.S.-Canadian consensus recommendations on the immunophenotypic analysis of hematologic neoplasia by flow cytometry: standardization and validation of laboratory procedures Cytometry 30:214230.[PubMed].[CrossRef]
26. Carter PH, Resto-Ruiz S, Washington GC, Ethridge S, Palini A, Vogt R, Waxdal M, Fleisher T, Noguchi PD, Marti GE. 1992. Flow cytometric analysis of whole blood lysis, three anticoagulants, and five cell preparations Cytometry 13:6874.[CrossRef].[PubMed]
27. Braylan RC, Benson NA. 1989. Flow cytometric analysis of lymphomas Arch Pathol Lab Med 113:627633.[PubMed]
28. Wood BL, Arroz M, Barnett D, DiGiuseppe J, Greig B, Kussick SJ, Oldaker T, Shenkin M, Stone E, Wallace P. 2007. 2006 Bethesda International Consensus recommendations on the immunophenotypic analysis of hematolymphoid neoplasia by flow cytometry: optimal reagents and reporting for the flow cytometric diagnosis of hematopoietic neoplasia Cytometry B Clin Cytom 72(Suppl 1):S1422.[CrossRef].[PubMed]
29. Wood BL. 2013. Flow cytometric monitoring of residual disease in acute leukemia Methods Mol Biol 999:123136.[CrossRef].[PubMed]
30. Wood B. 2006. 9-color and 10-color flow cytometry in the clinical laboratory Arch Pathol Lab Med 130:680690.[CrossRef].[PubMed]
31. Walter RB, Buckley SA, Pagel JM, Wood BL, Storer BE, Sandmaier BM, Fang M, Gyurkocza B, Delaney C, Radich JP, Estey EH, Appelbaum FR. 2013. Significance of minimal residual disease before myeloablative allogeneic hematopoietic cell transplantation for AML in first and second complete remission Blood 122:18131821.[CrossRef].[PubMed]
32. Campana D. 2008. Status of minimal residual disease testing in childhood haematological malignancies Br J Haematol 143:481489.[CrossRef].[PubMed]
33. Maurillo L, Buccisano F, Spagnoli A, Del Poeta G, Panetta P, Neri B, Del Principe MI, Mazzone C, Consalvo MI, Tamburini A, Ottaviani L, Fraboni D, Sarlo C, De Fabritiis P, Amadori S, Venditti A. 2007. Monitoring of minimal residual disease in adult acute myeloid leukemia using peripheral blood as an alternative source to bone marrow Haematologica 92:605611.[PubMed].[CrossRef]
34. Baer MR, Stewart CC, Dodge RK, Leget G, Sule N, Mrozek K, Schiffer CA, Powell BL, Kolitz JE, Moore JO, Stone RM, Davey FR, Carroll AJ, Larson RA, Bloomfield CD. 2001. High frequency of immunophenotype changes in acute myeloid leukemia at relapse: implications for residual disease detection (Cancer and Leukemia Group B Study 8361) Blood 97:35743580.[PubMed].[CrossRef]
35. Langebrake C, Brinkmann I, Teigler-Schlegel A, Creutzig U, Griesinger F, Puhlmann U, Reinhardt D. 2005. Immunophenotypic differences between diagnosis and relapse in childhood AML: implications for MRD monitoring Cytometry B Clin Cytom 63:19.[CrossRef].[PubMed]
36. Voskova D, Schoch C, Schnittger S, Hiddemann W, Haferlach T, Kern W. 2004. Stability of leukemia-associated aberrant immunophenotypes in patients with acute myeloid leukemia between diagnosis and relapse: comparison with cytomorphologic, cytogenetic, and molecular genetic findings Cytometry B Clin Cytom 62:2538.[CrossRef].[PubMed]
37. Kern W, Bacher U, Haferlach C, Schnittger S, Haferlach T. 2010. The role of multiparameter flow cytometry for disease monitoring in AML Best Pract Res Clin Haematol 23:379390.[CrossRef].[PubMed]
38. Karandikar NJ, Aquino DB, McKenna RW, Kroft SH. 2001. Transient myeloproliferative disorder and acute myeloid leukemia in Down syndrome. An immunophenotypic analysis Am J Clin Pathol 116:204210.[CrossRef].[PubMed]

Tables

Generic image for table
TABLE 1

Antigens commonly evaluated in the diagnosis of acute myeloid leukemia

Citation: Wood B, Soma L. 2016. Acute Myeloid Leukemia: Diagnosis and Minimal Residual Disease Detection by Flow Cytometry, p 217-225. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch22
Generic image for table
TABLE 2

Immunophenotypic characteristics associated with certain AML subtypes

Citation: Wood B, Soma L. 2016. Acute Myeloid Leukemia: Diagnosis and Minimal Residual Disease Detection by Flow Cytometry, p 217-225. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch22

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