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Published in: Annals of Hematology 6/2018

01-06-2018 | Review Article

An update on classification, genetics, and clinical approach to mixed phenotype acute leukemia (MPAL)

Authors: Maliha Khan, Rabbia Siddiqi, Kiran Naqvi

Published in: Annals of Hematology | Issue 6/2018

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Abstract

Mixed phenotype acute leukemia (MPAL) is an uncommon diagnosis, representing only about 2–5% of acute leukemia cases. The blast cells of MPAL express multilineage immunophenotypic markers and may have a shared B/T/myeloid phenotype. Due to historical ambiguity in the diagnosis of MPAL, the genetics and clinical features of this disease remain poorly characterized. Based on the 2008 and 2016 World Health Organization classifications, myeloid lineage is best determined by presence of myeloperoxidase, while B and T lymphoid lineages are demonstrated by CD19 and cytoplasmic CD3 expression. MPAL typically carries a worse prognosis than either acute myeloid leukemia (AML) or acute lymphoid leukemia (ALL). Given the rarity of MPAL, there is a lack of prospective trial data to guide therapy; treatment generally relies on ALL-like regimens followed by consolidation chemotherapy or hematopoietic stem cell transplant (HSCT). Here, we review the updated classification, biology, clinical features, and treatment approach to MPAL.
Literature
2.
go back to reference Altman AJ (1990) Clinical features and biological implications of acute mixed lineage (hybrid) leukemias. Am J Pediatr Hematol Oncol 12(2):123–133CrossRefPubMed Altman AJ (1990) Clinical features and biological implications of acute mixed lineage (hybrid) leukemias. Am J Pediatr Hematol Oncol 12(2):123–133CrossRefPubMed
3.
go back to reference Mirro J, Zipf TF, Pui CH, Kitchingman G, Williams D, Melvin S, Murphy SB, Stass S (1985) Acute mixed lineage leukemia: clinicopathologic correlations and prognostic significance. Blood 66(5):1115–1123PubMed Mirro J, Zipf TF, Pui CH, Kitchingman G, Williams D, Melvin S, Murphy SB, Stass S (1985) Acute mixed lineage leukemia: clinicopathologic correlations and prognostic significance. Blood 66(5):1115–1123PubMed
4.
go back to reference Sulak LE, Clare CN, Morale BA, Hansen KL, Montiel MM (1990) Biphenotypic acute leukemia in adults. Am J Clin Pathol 94(1):54–58CrossRefPubMed Sulak LE, Clare CN, Morale BA, Hansen KL, Montiel MM (1990) Biphenotypic acute leukemia in adults. Am J Clin Pathol 94(1):54–58CrossRefPubMed
5.
go back to reference Catovsky D, Matutes E, Buccheri V, Shetty V, Hanslip J, Yoshida N, Morilla R (1991) A classification of acute leukaemia for the 1990s. Ann Hematol 62(1):16–21CrossRefPubMed Catovsky D, Matutes E, Buccheri V, Shetty V, Hanslip J, Yoshida N, Morilla R (1991) A classification of acute leukaemia for the 1990s. Ann Hematol 62(1):16–21CrossRefPubMed
6.
go back to reference Bene MC, Bernier M, Casasnovas RO, Castoldi G, Knapp W, Lanza F, Ludwig WD, Matutes E, Orfao A, Sperling C, van’t Veer MB (1998) The reliability and specificity of c-kit for the diagnosis of acute myeloid leukemias and undifferentiated leukemias. The European Group for the Immunological Classification of Leukemias (EGIL). Blood 92(2):596–599PubMed Bene MC, Bernier M, Casasnovas RO, Castoldi G, Knapp W, Lanza F, Ludwig WD, Matutes E, Orfao A, Sperling C, van’t Veer MB (1998) The reliability and specificity of c-kit for the diagnosis of acute myeloid leukemias and undifferentiated leukemias. The European Group for the Immunological Classification of Leukemias (EGIL). Blood 92(2):596–599PubMed
7.
go back to reference Bene MC, Castoldi G, Knapp W, Ludwig WD, Matutes E, Orfao A, van’t Veer MB (1995) Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia 9(10):1783–1786PubMed Bene MC, Castoldi G, Knapp W, Ludwig WD, Matutes E, Orfao A, van’t Veer MB (1995) Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia 9(10):1783–1786PubMed
8.
go back to reference Jaffe E, Harris N, Stein HVJ, Vardiman JW (2001) Pathology and genetics of tumors of hematopoietic and lymphoid tissues, 2nd printing, World Health Organization classification of Tumours. IARC Press, Lyon, France Jaffe E, Harris N, Stein HVJ, Vardiman JW (2001) Pathology and genetics of tumors of hematopoietic and lymphoid tissues, 2nd printing, World Health Organization classification of Tumours. IARC Press, Lyon, France
9.
go back to reference Borowitz MJ, Bene MC, Harris NL, Porwit A, Matutes E (2008) Acute leukemias of ambiguous lineage. In: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press, Lyon, France Borowitz MJ, Bene MC, Harris NL, Porwit A, Matutes E (2008) Acute leukemias of ambiguous lineage. In: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press, Lyon, France
14.
15.
go back to reference Matutes E, Pickl WF, Van't Veer M, Morilla R, Swansbury J, Strobl H, Attarbaschi A, Hopfinger G, Ashley S, Bene MC, Porwit A, Orfao A, Lemez P, Schabath R, Ludwig WD (2011) Mixed-phenotype acute leukemia: clinical and laboratory features and outcome in 100 patients defined according to the WHO 2008 classification. Blood 117(11):3163–3171. https://doi.org/10.1182/blood-2010-10-314682 CrossRefPubMed Matutes E, Pickl WF, Van't Veer M, Morilla R, Swansbury J, Strobl H, Attarbaschi A, Hopfinger G, Ashley S, Bene MC, Porwit A, Orfao A, Lemez P, Schabath R, Ludwig WD (2011) Mixed-phenotype acute leukemia: clinical and laboratory features and outcome in 100 patients defined according to the WHO 2008 classification. Blood 117(11):3163–3171. https://​doi.​org/​10.​1182/​blood-2010-10-314682 CrossRefPubMed
21.
go back to reference Li S, Garrett-Bakelman FE, Chung SS, Sanders MA, Hricik T, Rapaport F, Patel J, Dillon R, Vijay P, Brown AL, Perl AE, Cannon J, Bullinger L, Luger S, Becker M, Lewis ID, To LB, Delwel R, Lowenberg B, Dohner H, Dohner K, Guzman ML, Hassane DC, Roboz GJ, Grimwade D, Valk PJ, D'Andrea RJ, Carroll M, Park CY, Neuberg D, Levine R, Melnick AM, Mason CE (2016) Distinct evolution and dynamics of epigenetic and genetic heterogeneity in acute myeloid leukemia. Nat Med 22(7):792–799. https://doi.org/10.1038/nm.4125 CrossRefPubMedPubMedCentral Li S, Garrett-Bakelman FE, Chung SS, Sanders MA, Hricik T, Rapaport F, Patel J, Dillon R, Vijay P, Brown AL, Perl AE, Cannon J, Bullinger L, Luger S, Becker M, Lewis ID, To LB, Delwel R, Lowenberg B, Dohner H, Dohner K, Guzman ML, Hassane DC, Roboz GJ, Grimwade D, Valk PJ, D'Andrea RJ, Carroll M, Park CY, Neuberg D, Levine R, Melnick AM, Mason CE (2016) Distinct evolution and dynamics of epigenetic and genetic heterogeneity in acute myeloid leukemia. Nat Med 22(7):792–799. https://​doi.​org/​10.​1038/​nm.​4125 CrossRefPubMedPubMedCentral
22.
go back to reference Heesch S, Neumann M, Schwartz S, Bartram I, Schlee C, Burmeister T, Hanel M, Ganser A, Heuser M, Wendtner CM, Berdel WE, Gokbuget N, Hoelzer D, Hofmann WK, Thiel E, Baldus CD (2013) Acute leukemias of ambiguous lineage in adults: molecular and clinical characterization. Ann Hematol 92(6):747–758. https://doi.org/10.1007/s00277-013-1694-4 CrossRefPubMed Heesch S, Neumann M, Schwartz S, Bartram I, Schlee C, Burmeister T, Hanel M, Ganser A, Heuser M, Wendtner CM, Berdel WE, Gokbuget N, Hoelzer D, Hofmann WK, Thiel E, Baldus CD (2013) Acute leukemias of ambiguous lineage in adults: molecular and clinical characterization. Ann Hematol 92(6):747–758. https://​doi.​org/​10.​1007/​s00277-013-1694-4 CrossRefPubMed
29.
go back to reference Kern W, Grossmann V, Roller A, Weissmann S, Alpermann T, Schoeck U, Haferlach C, Schnittger S, Haferlach T, Kohlmann A (2012) Mixed phenotype acute leukemia, T/myeloid, NOS (MPAL-TM) has a high <em>DNMT3A</em> mutation frequency and carries further genetic features of both AML and T-ALL: results of a comprehensive next-generation sequencing study analyzing 32 genes. Blood 120(21):403–403 Kern W, Grossmann V, Roller A, Weissmann S, Alpermann T, Schoeck U, Haferlach C, Schnittger S, Haferlach T, Kohlmann A (2012) Mixed phenotype acute leukemia, T/myeloid, NOS (MPAL-TM) has a high <em>DNMT3A</em> mutation frequency and carries further genetic features of both AML and T-ALL: results of a comprehensive next-generation sequencing study analyzing 32 genes. Blood 120(21):403–403
32.
go back to reference Neumann M, Heesch S, Schlee C, Schwartz S, Gokbuget N, Hoelzer D, Konstandin NP, Ksienzyk B, Vosberg S, Graf A, Krebs S, Blum H, Raff T, Bruggemann M, Hofmann WK, Hecht J, Bohlander SK, Greif PA, Baldus CD (2013) Whole-exome sequencing in adult ETP-ALL reveals a high rate of DNMT3A mutations. Blood 121(23):4749–4752. https://doi.org/10.1182/blood-2012-11-465138 CrossRefPubMed Neumann M, Heesch S, Schlee C, Schwartz S, Gokbuget N, Hoelzer D, Konstandin NP, Ksienzyk B, Vosberg S, Graf A, Krebs S, Blum H, Raff T, Bruggemann M, Hofmann WK, Hecht J, Bohlander SK, Greif PA, Baldus CD (2013) Whole-exome sequencing in adult ETP-ALL reveals a high rate of DNMT3A mutations. Blood 121(23):4749–4752. https://​doi.​org/​10.​1182/​blood-2012-11-465138 CrossRefPubMed
33.
go back to reference Zhang J, Ding L, Holmfeldt L, Wu G, Heatley SL, Payne-Turner D, Easton J, Chen X, Wang J, Rusch M, Lu C, Chen SC, Wei L, Collins-Underwood JR, Ma J, Roberts KG, Pounds SB, Ulyanov A, Becksfort J, Gupta P, Huether R, Kriwacki RW, Parker M, McGoldrick DJ, Zhao D, Alford D, Espy S, Bobba KC, Song G, Pei D, Cheng C, Roberts S, Barbato MI, Campana D, Coustan-Smith E, Shurtleff SA, Raimondi SC, Kleppe M, Cools J, Shimano KA, Hermiston ML, Doulatov S, Eppert K, Laurenti E, Notta F, Dick JE, Basso G, Hunger SP, Loh ML, Devidas M, Wood B, Winter S, Dunsmore KP, Fulton RS, Fulton LL, Hong X, Harris CC, Dooling DJ, Ochoa K, Johnson KJ, Obenauer JC, Evans WE, Pui CH, Naeve CW, Ley TJ, Mardis ER, Wilson RK, Downing JR, Mullighan CG (2012) The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature 481(7380):157–163. https://doi.org/10.1038/nature10725 CrossRefPubMedPubMedCentral Zhang J, Ding L, Holmfeldt L, Wu G, Heatley SL, Payne-Turner D, Easton J, Chen X, Wang J, Rusch M, Lu C, Chen SC, Wei L, Collins-Underwood JR, Ma J, Roberts KG, Pounds SB, Ulyanov A, Becksfort J, Gupta P, Huether R, Kriwacki RW, Parker M, McGoldrick DJ, Zhao D, Alford D, Espy S, Bobba KC, Song G, Pei D, Cheng C, Roberts S, Barbato MI, Campana D, Coustan-Smith E, Shurtleff SA, Raimondi SC, Kleppe M, Cools J, Shimano KA, Hermiston ML, Doulatov S, Eppert K, Laurenti E, Notta F, Dick JE, Basso G, Hunger SP, Loh ML, Devidas M, Wood B, Winter S, Dunsmore KP, Fulton RS, Fulton LL, Hong X, Harris CC, Dooling DJ, Ochoa K, Johnson KJ, Obenauer JC, Evans WE, Pui CH, Naeve CW, Ley TJ, Mardis ER, Wilson RK, Downing JR, Mullighan CG (2012) The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature 481(7380):157–163. https://​doi.​org/​10.​1038/​nature10725 CrossRefPubMedPubMedCentral
36.
go back to reference Killick S, Matutes E, Powles RL, Hamblin M, Swansbury J, Treleaven JG, Zomas A, Atra A, Catovsky D (1999) Outcome of biphenotypic acute leukemia. Haematologica 84(8):699–706PubMed Killick S, Matutes E, Powles RL, Hamblin M, Swansbury J, Treleaven JG, Zomas A, Atra A, Catovsky D (1999) Outcome of biphenotypic acute leukemia. Haematologica 84(8):699–706PubMed
38.
go back to reference Legrand O, Perrot JY, Simonin G, Baudard M, Cadiou M, Blanc C, Ramond S, Viguie F, Marie JP, Zittoun R (1998) Adult biphenotypic acute leukaemia: an entity with poor prognosis which is related to unfavourable cytogenetics and P-glycoprotein over-expression. Br J Haematol 100(1):147–155CrossRefPubMed Legrand O, Perrot JY, Simonin G, Baudard M, Cadiou M, Blanc C, Ramond S, Viguie F, Marie JP, Zittoun R (1998) Adult biphenotypic acute leukaemia: an entity with poor prognosis which is related to unfavourable cytogenetics and P-glycoprotein over-expression. Br J Haematol 100(1):147–155CrossRefPubMed
39.
go back to reference Lee JH, Min YH, Chung CW, Kim BK, Yoon HJ, Jo DY, Shin HJ, Bang SM, Won JH, Zang DY, Kim HJ, Chi HS, Lee KH, Cheong JW, Kim JS, Kim SH, Park S, Park SY, Chung JS, Lee JH, Park CJ, Korean Society of Hematology AMLMDSWP (2008) Prognostic implications of the immunophenotype in biphenotypic acute leukemia. Leuk Lymphoma 49(4):700–709. https://doi.org/10.1080/10428190701843247 CrossRefPubMed Lee JH, Min YH, Chung CW, Kim BK, Yoon HJ, Jo DY, Shin HJ, Bang SM, Won JH, Zang DY, Kim HJ, Chi HS, Lee KH, Cheong JW, Kim JS, Kim SH, Park S, Park SY, Chung JS, Lee JH, Park CJ, Korean Society of Hematology AMLMDSWP (2008) Prognostic implications of the immunophenotype in biphenotypic acute leukemia. Leuk Lymphoma 49(4):700–709. https://​doi.​org/​10.​1080/​1042819070184324​7 CrossRefPubMed
41.
go back to reference Deffis-Court M, Alvarado-Ibarra M, Ruiz-Arguelles GJ, Rosas-Lopez A, Barrera-Lumbreras G, Aguayo-Gonzalez A, Lopez-Karpovitch X, Lopez-Hernandez M, Velazquez-Sanchez de Cima S, Zamora-Ortiz G, Crespo-Solis E (2014) Diagnosing and treating mixed phenotype acute leukemia: a multicenter 10-year experience in Mexico. Ann Hematol 93(4):595–601. https://doi.org/10.1007/s00277-013-1919-6 CrossRefPubMed Deffis-Court M, Alvarado-Ibarra M, Ruiz-Arguelles GJ, Rosas-Lopez A, Barrera-Lumbreras G, Aguayo-Gonzalez A, Lopez-Karpovitch X, Lopez-Hernandez M, Velazquez-Sanchez de Cima S, Zamora-Ortiz G, Crespo-Solis E (2014) Diagnosing and treating mixed phenotype acute leukemia: a multicenter 10-year experience in Mexico. Ann Hematol 93(4):595–601. https://​doi.​org/​10.​1007/​s00277-013-1919-6 CrossRefPubMed
50.
go back to reference Shimizu H, Saitoh T, Machida S, Kako S, Doki N, Mori T, Sakura T, Kanda Y, Kanamori H, Miyawaki S, Okamoto S, Kanto Study Group for Cell T (2015) Allogeneic hematopoietic stem cell transplantation for adult patients with mixed phenotype acute leukemia: results of a matched-pair analysis. Eur J Haematol 95(5):455–460. https://doi.org/10.1111/ejh.12516 CrossRefPubMed Shimizu H, Saitoh T, Machida S, Kako S, Doki N, Mori T, Sakura T, Kanda Y, Kanamori H, Miyawaki S, Okamoto S, Kanto Study Group for Cell T (2015) Allogeneic hematopoietic stem cell transplantation for adult patients with mixed phenotype acute leukemia: results of a matched-pair analysis. Eur J Haematol 95(5):455–460. https://​doi.​org/​10.​1111/​ejh.​12516 CrossRefPubMed
52.
54.
go back to reference DeAngelo DJ, Stevenson KE, Dahlberg SE, Silverman LB, Couban S, Supko JG, Amrein PC, Ballen KK, Seftel MD, Turner AR, Leber B, Howson-Jan K, Kelly K, Cohen S, Matthews JH, Savoie L, Wadleigh M, Sirulnik LA, Galinsky I, Neuberg DS, Sallan SE, Stone RM (2015) Long-term outcome of a pediatric-inspired regimen used for adults aged 18-50 years with newly diagnosed acute lymphoblastic leukemia. Leukemia 29(3):526–534. https://doi.org/10.1038/leu.2014.229 CrossRefPubMed DeAngelo DJ, Stevenson KE, Dahlberg SE, Silverman LB, Couban S, Supko JG, Amrein PC, Ballen KK, Seftel MD, Turner AR, Leber B, Howson-Jan K, Kelly K, Cohen S, Matthews JH, Savoie L, Wadleigh M, Sirulnik LA, Galinsky I, Neuberg DS, Sallan SE, Stone RM (2015) Long-term outcome of a pediatric-inspired regimen used for adults aged 18-50 years with newly diagnosed acute lymphoblastic leukemia. Leukemia 29(3):526–534. https://​doi.​org/​10.​1038/​leu.​2014.​229 CrossRefPubMed
55.
go back to reference Larson RA, Dodge RK, Burns CP, Lee EJ, Stone RM, Schulman P, Duggan D, Davey FR, Sobol RE, Frankel SR et al (1995) A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B study 8811. Blood 85(8):2025–2037PubMed Larson RA, Dodge RK, Burns CP, Lee EJ, Stone RM, Schulman P, Duggan D, Davey FR, Sobol RE, Frankel SR et al (1995) A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B study 8811. Blood 85(8):2025–2037PubMed
58.
60.
go back to reference Zhao XF, Gojo I, York T, Ning Y, Baer MR (2009) Diagnosis of biphenotypic acute leukemia: a paradigmatic approach. Int J Clin Exp Pathol 3(1):75–86PubMed Zhao XF, Gojo I, York T, Ning Y, Baer MR (2009) Diagnosis of biphenotypic acute leukemia: a paradigmatic approach. Int J Clin Exp Pathol 3(1):75–86PubMed
61.
go back to reference Carbonell F, Swansbury J, Min T, Matutes E, Farahat N, Buccheri V, Morilla R, Secker-Walker L, Catovsky D (1996) Cytogenetic findings in acute biphenotypic leukaemia. Leukemia 10(8):1283–1287PubMed Carbonell F, Swansbury J, Min T, Matutes E, Farahat N, Buccheri V, Morilla R, Secker-Walker L, Catovsky D (1996) Cytogenetic findings in acute biphenotypic leukaemia. Leukemia 10(8):1283–1287PubMed
62.
go back to reference Buccheri V, Matutes E, Dyer MJ, Catovsky D (1993) Lineage commitment in biphenotypic acute leukemia. Leukemia 7(6):919–927PubMed Buccheri V, Matutes E, Dyer MJ, Catovsky D (1993) Lineage commitment in biphenotypic acute leukemia. Leukemia 7(6):919–927PubMed
Metadata
Title
An update on classification, genetics, and clinical approach to mixed phenotype acute leukemia (MPAL)
Authors
Maliha Khan
Rabbia Siddiqi
Kiran Naqvi
Publication date
01-06-2018
Publisher
Springer Berlin Heidelberg
Published in
Annals of Hematology / Issue 6/2018
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-018-3297-6

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