Clinical and Experimental Medicine

, Volume 18, Issue 4, pp 513–521 | Cite as

Mixed-phenotype acute leukemia characteristics: first report from Iran

  • Behzad PoopakEmail author
  • Adnan Khosravi
  • Gholamreza Bahoush-Mehdiabadi
  • Tahereh Madani
  • Elahe Khodadi
  • Zohreh Farahani
  • Amir Ali Vahedi
  • Gelareh Khosravipour
  • Peyvand Poopak
  • Amir Hossein Poopak
Original Article


Mixed-phenotype acute leukemia (MPAL) is the infrequent type of acute leukemia characterized by immunophenotypic and/or cytochemical features of both lineages, but the diagnosis of this disease still is a challenge. In this study, we analyzed immunophenotyping, cytochemistry and frequency of MPAL patients to better diagnosis of MPAL characteristics according to WHO 2016 criteria for the first time in Iran. In this retrospective study, 27 patients were diagnosed as MPAL based on WHO 2016 criteria during 2014–2017. Flow cytometric immunophenotyping was performed on PB and BM samples evaluation of different CD marker expressions in MPAL subsets. RT-PCR was performed for the analyses of BCR/ABL1 fusion in MPAL subsets. Among 27 cases, (70.4%) 19 cases were B + My, (22.22%) 6 cases were T + My, and 2 cases (7.40%) were B + T + My. CD34, CD19, HLA-DR, TdT, CD22, iMPO were positive in majority of B + My cases. CD45, iMPO, iCD3, CD7, CD2 and CD5 were positive in majority of T + My cases. HLA-DR, TdT, CD10, CD22, iCD79a, iMPO, CD45, iCD3, CD7, CD3, CD2, CD5 were positive in majority of B + T + My cases. BCR/ABL1 fusion was positive for 3 cases (11.1%) of p190 fusion and 2 cases (7.4%) of p210 fusion in B + My cases. WHO 2016 criteria are the current standard for diagnosing MPAL. Also, evaluation of TdT, CD2, CD5, CD7 expressions by flow cytometry in EGIL criteria is useful for the better diagnosis of MPAL subsets. In addition, evaluation of BCR/ABL1 and MLL rearrangements in patients should be part of standard work-up in MPAL.


Mixed-phenotype acute leukemia Flow cytometry BCR/ABL1 



This work was financially supported by Payvand Clinical and Specialty Laboratory, Tehran, Iran.

Authors’ contributions

BP conceived the manuscript and revised it. EK, GK and PP wrote the manuscript; AHE provided clinical data and pathological diagnoses; TM, ZF, AAV and AHP performed the technical tests.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Human and animal rights

All the procedures performed in the studies involving human participants were in accordance with the ethical standards of 1964 Helsinki Declaration.

Informed consent

Written informed consent was obtained from all patients and normal subjects.


  1. 1.
    Wolach O, Stone RM. How I treat mixed-phenotype acute leukemia. Blood. 2015;125(16):2477–85.CrossRefGoogle Scholar
  2. 2.
    Golchin N, Khodadi E, Yaghooti SH, Jaseb K, Shahjahani M, Tavakolifar Y, et al. Immunophenotype, microRNA expression and cytogenetic characterization of acute leukemias of ambiguous lineage. Comp Clin Pathol. 2017;26(2):261–7.CrossRefGoogle Scholar
  3. 3.
    Getta BM, Roshal M, Zheng J, Park JH, Stein EM, Levine R, et al. Allogeneic hematopoietic stem cell transplantation with myeloablative conditioning is associated with favorable outcomes in mixed phenotype acute leukemia. Biol Blood Marrow Transplant. 2017;23:1879–86.CrossRefGoogle Scholar
  4. 4.
    Kim HJ. Mixed-phenotype acute leukemia (MPAL) and beyond. Blood Res. 2016;51(4):215–6.CrossRefGoogle Scholar
  5. 5.
    Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114(5):937–51.CrossRefGoogle Scholar
  6. 6.
    Porwit A, Bene MC. Acute leukemias of ambiguous origin. Am J Clin Pathol. 2015;144:361–76.CrossRefGoogle Scholar
  7. 7.
    Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391–405.CrossRefGoogle Scholar
  8. 8.
    Weinberg OK, Arber DA. Mixed-phenotype acute leukemia: historical overview and a new definition. Leukemia. 2010;24:1844–51.CrossRefGoogle Scholar
  9. 9.
    Gisslinger H, Jeryczynski G, Gisslinger B, Wölfler A, Burgstaller S, Buxhofer-Ausch V, et al. Clinical impact of bone marrow morphology for the diagnosis of essential thrombocythemia: comparison between the BCSH and the WHO criteria. Leukemia. 2016;30(5):1126.CrossRefGoogle Scholar
  10. 10.
    Donghen JJV, Macintyre EA, Gabert JA, Delabesse E, Rossi V, Saglio G. Standardized RT-PCR analysis of fusion gene transcripts from chromosome aberrations in acute leukemia for detection of minimal residual disease. Report of the BIOMED-1 Concerted Action: investigation of minimal residual disease in acute leukemia. Leukemia. 1999;13:1901–28.CrossRefGoogle Scholar
  11. 11.
    Yan L, Ping N, Zhu M, Sun A, Xue Y, Ruan C, et al. Clinical, immunophenotypic, cytogenetic, and molecular genetic features in 117 adult patients with mixed-phenotype acute leukemia defined by WHO-2008 classification. Haematologica. 2012;97(11):1708–12.CrossRefGoogle Scholar
  12. 12.
    Matutes E, Pickl WF, van’t Veer M, Morilla R, Swansbury J, Strobl H, et al. Mixed-phenotype acute leukemia: clinical and laboratory features and outcome in 100 patients defined according to the WHO 2008 classification. Blood. 2011;117(11):3163–71.CrossRefGoogle Scholar
  13. 13.
    van den Ancker W, Westers TM, de Leeuw DC, van der Veeken YF, Loonen A, van Beckhoven E, et al. A threshold of 10% for myeloperoxidase by flow cytometry is valid to classify acute leukemia of ambiguous and myeloid origin. Cytom Part B Clin Cytom. 2013;84(2):114–8.CrossRefGoogle Scholar
  14. 14.
    Oberley MJ, Li S, Orgel E, Phei Wee C, Hagiya A, O’Gorman MR. Clinical significance of isolated myeloperoxidase expression in pediatric B-lymphoblastic leukemia. Am J Clin Pathol. 2017;147(4):374–81.CrossRefGoogle Scholar
  15. 15.
    Raikar SS, Park SI, Leong T, Jaye DL, Keller FG, Horan JT, Woods WG. Isolated myeloperoxidase expression in pediatric B/myeloid mixed phenotype acute leukemia is linked with better survival. Blood. 2018;131(5):573–7.CrossRefGoogle Scholar
  16. 16.
    Al-Seraihy AS, Owaidah TM, Ayas M, El-Solh H, Al-Mahr M, Al-Ahmari A, et al. Clinical characteristics and outcome of children with biphenotypic acute leukemia. Haematologica. 2009;94(12):1682–90.CrossRefGoogle Scholar
  17. 17.
    Wang Y, Gu M, Mi Y, Qiu L, Bian S, Wang J. Clinical characteristics and outcomes of mixed phenotype acute leukemia with Philadelphia chromosome positive and/or BCR-ABL positive in adult. Int J Hematol. 2011;94(6):552–5.CrossRefGoogle Scholar
  18. 18.
    Borowitz MJ, Bene MC, Harris NL, et al. Acute leukemias of ambiguous lineage. In: WHO classification of tumours of haematopoietic and lymphoid tissues. IARC Press; 2008. p. 150–155.Google Scholar
  19. 19.
    Deffis-Court MA-IM, Ruiz-Argüelles GJ, Rosas-López A, Barrera-Lumbreras G, Aguayo-González A, López-Karpovitch X, López-Hernández M, Velázquez-Sánchez de Cima S, Zamora-Ortiz G, Crespo-Solís E, et al. Diagnosing and treating mixed phenotype acute leukemia: a multicenter 10-year experience in México. Ann Hematol. 2014;93:595–601.CrossRefGoogle Scholar
  20. 20.
    Quesada AE, Hu Z, Routbort MJ, Patel KP, Luthra R, Loghavi S, et al. Mixed phenotype acute leukemia contains heterogeneous genetic mutations by next-generation sequencing. Oncotarget. 2018;9(9):8441–9.CrossRefGoogle Scholar
  21. 21.
    Kawajiri C, Tanaka H, Hashimoto S, Takeda Y, Sakai S, Takagi T, et al. Successful treatment of Philadelphia chromosome-positive mixed phenotype acute leukemia by appropriate alternation of second-generation tyrosine kinase inhibitors according to BCRABL1 mutation status. Int J Hematol. 2014;99(4):513–8.CrossRefGoogle Scholar
  22. 22.
    Rubnitz JE, Onciu M, Pounds S, Shurtleff S, Cao X, Raimondi SC, Behm FG, Campana D, Razzouk BI, Ribeiro RC, Downing JR. Acute mixed lineage leukemia in children: the experience of St Jude Children’s Research Hospital. Blood. 2009;113(21):5083–9.CrossRefGoogle Scholar
  23. 23.
    Zhang Y, Wu D, Sun A, Qiu H, He G, Jin Z, Tang X, Miao M, Fu Z, Han Y. Clinical characteristics, biological profile, and outcome of biphenotypic acute leukemia: a case series. Acta Haematol. 2011;125(4):210–8.CrossRefGoogle Scholar
  24. 24.
    Charles NJ, Boyer DF. Mixed-phenotype acute leukemia: diagnostic criteria and pitfalls. Arch Pathol Lab Med. 2017;141(11):1462–8.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Behzad Poopak
    • 1
    • 2
    Email author
  • Adnan Khosravi
    • 3
  • Gholamreza Bahoush-Mehdiabadi
    • 4
  • Tahereh Madani
    • 2
  • Elahe Khodadi
    • 2
  • Zohreh Farahani
    • 2
  • Amir Ali Vahedi
    • 2
  • Gelareh Khosravipour
    • 2
  • Peyvand Poopak
    • 2
  • Amir Hossein Poopak
    • 2
  1. 1.Islamic Azad University, Tehran Medical Sciences BranchTehranIran
  2. 2.Payvand Clinical and Specialty LaboratoryTehranIran
  3. 3.Department of Pediatrics, Ali Asghar Pediatric HospitalIran University of Medical SciencesTehranIran
  4. 4.Tobacco Prevention and Control Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD)Shahid Beheshti University of Medical SciencesTehranIran

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