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Park, Chae, Kim, Lim, Kim, Lee, Chung, Cho, Kim, Lee, and Han: A Study of Mixed Phenotype Acute Leukemia Based on the 2008 World Health Organization Classification
Original Article

Korean J Leg Med 2010;30(6):525-532.

Published online: 14 January 2010

DOI: https://doi.org/10.3343/kjlm.2010.30.6.525

A Study of Mixed Phenotype Acute Leukemia Based on the 2008 World Health Organization Classification

Joonhong Park, M.D.1, Hyojin Chae, M.D.1, Myungshin Kim, M.D.1, Jihyang Lim, M.D.1, Yonggoo Kim, M.D.1, Jaewook Lee, M.D.2, Nak Gyun Chung, M.D.2, Bin Cho, M.D.2, Hack Ki Kim, M.D.2, Seok Lee, M.D.3, Kyungja Han, M.D.1

1Departments of Laboratory Medicine, Seoul, Korea

2Departments of Pediatrics, Seoul, Korea

3Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea

Corresponding author: Kyungja Han, M.D. Department of Laboratory Medicine, Seoul St. Mary's Hospital, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea Tel: +82-2-2258-1644, Fax: +82-2-2258-1719 E-mail: hankja@catholic.ac.kr

      Revised 18 March 201027 September 2010       Accepted 12 October 2010

Copyright © 2010 Korean Society for Legal Medicine

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background:

We evaluated the clinical significance of revised 2008 WHO classification needed to diagnose mixed phenotype acute leukemia (MPAL).

Methods:

A total of 22 MPAL patients, previously diagnosed by applying the scoring system of the European Group for Immunological Classification of Acute Leukemias (EGIL) were reclassified based on the 2008 WHO classification.

Results:

In 2008 WHO classification, the number of monoclonal antibodies (mAbs) required for assigning more than one lineage was markedly decreased, from 26 to 11, compared with that of EGIL. Seventeen of the 22 MPAL patients were reclassified as MPAL with following details: 6 MPAL with t(9;22)(q34;q11.2); BCR-ABL1, 1 MPAL with t(v;11q23); MLL rearranged, 7 MPAL, B/Myeloid, not otherwise specified (NOS) and 3 MPAL, T/Myeloid, NOS. Five patients were excluded from MPAL in the revised classification: 4 cytoplasmic myeloperoxidase (cMPO)-negative and 1 CD19-negative. The failure of complete remission achievement and occurrence of relapse were associated with poor prognosis (P=0.0002 and P=0.009, respectively). But the presence of Philadelphia chromsome was not significantly related with patient outcome (P=0.082). One patient with cCD79a, CD20, CD38, cMPO and CD15, whose diagnosis was reclassified from MPAL to AML has survived during the study period.

Conclusions:

Because of decreased number of mAbs needed, it is possible that acute leukemia panel is designed to include all mAbs required to diagnose MPAL according to 2008 WHO classification. When diagnosing MPAL, it is critical to figure out positivity in either cMPO or CD19, and AML expressing more than 2 lymphoid antigens are considered as MPAL.

Keywords: Mixed phenotype acute leukemia (MPAL), 2008 WHO classification, Reclassification

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Table 1.
Requirements for assigning more than one lineage to a single blast population [7]
Myeloid lineage
Myeloperoxidase (flow cytometry, immunohistochemistry or cytochemistry) or monocytic differentiation (at least 2 of the following: NSE, CD11c, CD14, CD64, lysozyme)
B lineage∗
Strong CD19 with at least 1 of the following strongly expressed: CD79a, cCD22, CD10 or weak CD19 with at least 2 of the following strongly expressed: CD79a, cCD22, CD10
T lineage
cCD3 (flow cytometry with antibodies to CD3 epsilon chain; immuno-histochemistry using polyclonal anti-CD3 antibody may detect CD3 zeta chain, which is not T-cell specific) or Surface CD3 (rare in mixed phenotype acute leukemias)

∗ Multiple antigens required.

Table 2.
Treatment and prognosis in total 22 patients
No. case Sex/Age Chromosome study ALGST CR Post-remission therapy Relapse Survival
1 M/9 47,XY,+X[15]/46,XY[5] Negative CR CTx NR Alive (59+d)
2 M/10 46,XY,t(9;22)(q34;q11.2)[10]/46,XY[10] t(9;22)-BCR/ABL e1a2 NCR - - Died (41d)
3 M/31 47,XY,t(10;11)(p13;q21),del(13)(q12q14),t(17;19)(q11.2;p13.3), +der(19)t(17;19)[12]/46,XY[8] Negative CR CTx, Allo-BMT NR Alive (188+d)
4 F/34 46,XX,inv(7)(p15q34)[5]/46,XX[15] Negative NCR - - Alive (223+d)
5 M/50 46,XY,t(4;11)(q21;q23)[20] t(4;11)-MLL1/AF4 CR CTx, Allo-BMT R(183d) Alive (316+d)
6 M/22 71<3n>,XXY,+2,t(2;7)(p10;p10)x2,+5,-7,+8,-9,t(9;22)(q34;q11.2)x2,+10,+17,-18,-20[cp12]/46,XY[8] t(9;22)-BCR/ABL e1a2 CR CTx, Auto-BMT NR Alive (391+d)
7 M/65 39~41,XY,-3,-4,del(5)(q13q22),-6,-7,del(8)(q22),-9,-16,-17, −18,add(19)(q13.4),-20,dup(21)(q11.2q22),+1~3mar[cp20] Negative CR CTx R(213d) Died (222d)
8 M/9 46,XY[20] Negative CR CTx NR Alive (395+d)
9 F/11 46,XX[20] Negative CR CTx NR Alive (430+d)
10 M/37 46,XY[20] Negative CR CTx, Auto-PBSCT R(121d) Alive (450+d)
11 M/1 N/A Negative NCR - - Died (24d)
12 F/53 45,XX,-7,t(9;22)(q34;q11.2)[20] t(9;22)-BCR/ABL e1a2 CR CTx R(213d) Died (246d)
13 M/43 46,XY,t(9;22)(q34;q11.2)[29]/46,XY[1] N/A CR CTx R(298d) Alive (729+d)
14 M/60 46,XY,t(9;22)(q34;q11.2)[7]/46,XY[13] t(9;22)-BCR/ABL e1a2 CR CTx R(61d) Died (69d)
15 F/57 46,XX,der(5)t(5;9),der(9)t(9;22),der(22)t(9;22);(q34q11.2) t(5;9)(q13;q34)[20] N/A CR CTx R(153d) Died (179d)
16 M/8 56,XY,+X,del(4)(q27q32),+der(4)t(1;4)(q12;q35),+6,+8,+10, +11,+14,+18,+21×2[cp10]/46,XY[10] N/A CR CTx, Auto-PBSCT NR Alive (874+d)
17 M/46 46,XY[20] N/A NCR - - Died (45d)
18 F/63 46,XX[20] N/A CR CTx R(92d) Died (356d)
19 M/13 46,XY,-5,t(9;22)(q34;q11.2),+1~2r[cp20] N/A NCR - - Died (14d)
20 M/6 46,XY,del(12)(p13),t(12;21)(p13;q22)[8]/46,XY[12] N/A CR CTx NR Alive (1086+d)
21 F/9 46,XX,del(6)(q21),del(12)(p13),t(12;21)(p13;q22)[15]/46,XX[5] N/A CR CTx NR Alive (1137+d)
22 F/58 87~90,XXXX,del(1)(p22p36.1),del(2)(q33),der(2)t(2;?)t(2;?)(q31;?),dic(7;18)(p13;p11.3)x2[cp17]/46,XX[3] N/A CR CTx R(214d) Died (344d)

Abbreviations: ALGST, acute leukemia gene screening test; CR, complete remission; CTx, chemotherapy; NR, no relapse; NCR, no complete remission; Allo-BMT, allogeneic bone marrow transplantation; R, relapse; Auto-BMT, autologous BMT; Auto-PBSCT, autologous peripheral blood stem cell transplantation; N/A, not available.

Table 3.
Expression of immunophenotypic markers on leukemic blasts in total 22 patients
No. case Myeloid lineage B lineage T lineage Diagnosis
cMPO NSE CD11c CD14 CD64 Lysozyme CD19 CD79a cCD22 CD10 cCD3 CD3
1 + - N/A - N/A N/A S+ S+ N/A S+ - - B/MY, NOS
2 + - N/A - N/A N/A S+ S+ N/A S+ - - MPAL c t(9;22)
3 + - N/A - N/A N/A W+ S+ +∗ - - - MPAL c t(v;11q23)
4 + - N/A - N/A N/A W+ W+ +∗ - - - B/MY, NOS
5 + - N/A - N/A N/A - W+ N/A - - - AML
6 + - N/A - N/A N/A S+ S+ N/A S+ - - MPAL c t(9;22)
7 + - N/A - N/A N/A S+ S+ N/A - - - B/MY, NOS
8 + - N/A - N/A N/A S+ S+ N/A W+ - - B/MY, NOS
9 + - N/A - N/A N/A S+ S+ N/A S+ - - B/MY, NOS
10 + - N/A + N/A N/A - - N/A - + - T/MY, NOS
11 - - N/A - - N/A - N/A - - + N/A T-ALL
12 + - N/A - - N/A W+ N/A W+ S+ - N/A MPAL c t(9;22)
13 + - N/A - - N/A S+ +∗ W+ - - N/A MPAL c t(9;22)
14 + - N/A - - N/A S+ N/A S+ W+ - N/A MPAL c t(9;22)
15 - - N/A - - N/A W+ N/A W+ W+ - N/A B-ALL c t(9;22)
16 + - N/A - + N/A S+ N/A W+ S+ - N/A B/MY, NOS
17 + - N/A - - N/A - N/A - - + N/A T/MY, NOS
18 - - N/A - - N/A - N/A - - + N/A T-ALL
19 + - N/A - - N/A W+ +∗ W+ - - N/A MPAL c t(9;22)
20 + - N/A - - N/A S+ N/A S+ W+ - N/A B/MY, NOS
21 - - N/A - - N/A S+ N/A S+ S+ - N/A B-ALL
22 + - N/A - - N/A - N/A - - + N/A T/MY, NOS

∗ Immunohistochemical stains done.

Abbreviations: cMPO, cytoplasmic myeloperoxidase; NSE, nonspecific esterase; +, positive; -, negative; N/A, not available; S+, strong positive; B/MY, NOS, MPAL, B/Myeloid, not otherwise specified (NOS); MPAL c t(9;22), MPAL with t(9;22)(q34;q11.2); BCR-ABL1; W+, weak positive; MPAL c t(v;11q23), MPAL with t(v;11q23); MLL rearranged; T/MY, NOS, MPAL, T/Myeloid, NOS; T-ALL, T lymphoblastic leukemia/lymphoma; B-ALL c t(9;22), B lymphoblastic leukemia/lymphoma with t(9;22)(q34;q11.); BCR-ABL1.

Table 4.
Annual update of immunological markers of flow cytometry
Annual Lineages
Myeloid B lymphoid T lymphoid
2009 (present) CD117, CD64, CD33, CD13, CD11c, cMPO cCD79a, CD20, CD19, CD10, cCD22 CD7, CD5, CD2, cCD3
2008 CD117, CD33, CD15, CD14, CD13, cMPO CD38, CD20, CD19, CD10, sur-λ, sur-κ, cy-μ, cCD79a CD8, CD7, CD5, CD4, CD3, CD2, cCD3
2007 CD117, CD64, CD33, CD14, CD13, cMPO CD20, CD19, CD10, cCD22 CD7, CD5, cCD3
2006 CD117, CD64, CD33, CD14, CD13, cMPO CD20, CD19, CD10, sur-λ, sur-κ, cy-μ, cCD22 CD8, CD7, CD5, CD4, CD2, cCD3

Abbreviations: cMPO, cytoplasmic myeloperoxidase; cCD22, cytoplasmic CD22; sur-λ, surface λ; sur-κ, surface κ; cy-μ, cytoplasmic IgM; cCD79a, cytoplasmic CD79a; cCD3, cytoplasmic CD3.

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