Combined two categories (Biphenotypic and Bilineage)
Created 6 new categories
MPAL T/myeloid NOS MPAL with t(9;22) BCR-ABL1 MPAL with t(v;11q23) MLL rearr MPAL B/myeloid NOS No lineage-specific antigens Other Separate blast populations of different lineages OR One blast population expressing antigens >1 lineage Mixed phenotype acute leukemia (MPAL) Acute leukemias of ambiguous lineage Antigens of > 1 lineage With additional genetic abnormalities Acute undifferentiated leukemia
European Group for the Immunological Characterization of Leukemias (EGIL)
B Lymphoid Markers in AML
CD7 and TdT expression in AML is well known
CD79a expression in AML
Cruse 2005: 4/46 (8.7%)
Tiacci 2004: 10/160 (1.6%)
El-Sissy 2006: 1/34 (2.9%)
Tiacci 2004: 10/160 (1.6%)
El-Sissy 2006 4/34 (11%)
CD22 (EGIL score 2)
El-Sissy 2006 1/34 (2.9%)
Lymphoid markers in AML
More than 30% show PAX5 expression
Pax5 in t(8;21) Gibson, 2006
AML with cytogenetic abnormalities
AML with inv(16) or t(16;16)
AML with t(15;17)
CD2 expression in microgranular variant
AML with t(6;9)
50% TdT expression
M1 and M2 (AML, NOS)
10-20% positive for CD2, CD4, CD19, or CD56
American Society of Hematopathology Image Bank
Aberrant Markers in ALL
Park et al , 1992
137 ALL cases in adults
Phenotyped by immunofluoresence
B-ALL more often
CD13 (1%) and CD33 (2%)
CD2 (1%) and CD5 (1%)
Myeloid markers in ALL
Kalina et al , 2005
381 B-ALL pediatric patients
Flow cytometric immunophenotyping
Vitale et al , 2007
374 adult ALL patients
Flow cytometric immunophenotyping of CD13 and/or CD33
Myeloid Markers in ALL
MPO in pediatric ALL
Austin 1998: (COG) 32/57 (56%) pediatric ALL expressed MPO at protein or mRNA level
All cases negative for t(9;22)
MPO in adult ALL
Arber 2001: 19/67 (23%) positive
8/19 (42%) with bcr/abl
Polyclonal MPO antibody
Immunocytochemistry with monoclonal MPO negative
pMPO in ALL, Arber 2001
Most specific lineage markers
Distinctly difficult to find lymphoblastic leukemias with aberrant MPO
Burkitt like ALL
Myeloid leukemia with aberrant CD3 also distinctly uncommon
B cell markers seem to be most promiscuous
MPO OR At least 2 : NSE CD11c CD14 CD64 lysozyme
Cytoplasmic CD3 OR Rare in MPAL
At least ONE (strong) :
Strong CD19 OR + At least TWO (strong) : CD79a Cytoplasmic CD22 CD10
MPAL - Exclusions
recurrent AML-associated translocations
- t(8;21) – freq expresses B cell markers
- inv (16)
FGFR1 mutation associated leukemias
CML blast crisis
Case Presentation #2
47 year old male with cellulitis
Transferred to University of Michigan for pancytopenia and blasts on blood smear
Arber, Daniel et al . Myeloperoxidase Immunoreactivity in Adult Acute Lymphoblastic Leukemia. Am J Clin Pathol 2001;116:25-33.
Austin G et al . Prevalence of myeloperoxidase gene expression in infant acute lymphocytic leukemia. Am J Clin Pathol . 1998;110:575-581.
Cruse, Julius et al . Aberrant expression of CD7, CD56, and CD79a antigens in acute myeloid leukemias. Experimental and Molecular Pathology 79 (2005) 39– 41.
El-Sissy et al . Aberrant Lymphoid Antigen Expression in Acute Myeloid Leukemia in Saudi Arabia. Journal of the Egyptian Nat. Cancer Inst., Vol. 18, No. 3, September: 244-249, 2006.
Gibson, et al. Expression of the B Cell–Associated Transcription Factors PAX5, OCT-2, and BOB.1 in Acute Myeloid Leukemia. Associations With B-Cell Antigen Expression and Myelomonocytic Maturation. Am J Clin Pathol 2006;126:916-924.
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Park et al. Acute Leukemias with Unusual Phenotypes. Journal of Korean Medical Science. 7(4), 377-384, 1992.
Preti A, Huh YO, O'Brien SM, et al: Myeloid markers in adult acute lymphocytic leukemia. Cancer 76:1564, 1995.
Tiacci et al . PAX5 Expression in Acute Leukemias: Higher B-Lineage Specificity Than CD79a and Selective Association with t(8;21)-Acute Myelogenous Leukemia. Cancer Research. 64, 7399–7404, October 15, 2004
Valbuena, Jose et al . Expression of B Cell–Specific Activator Protein/PAX5 in Acute Myeloid Leukemia With t(8;21)(q22;q22). Am J Clin Pathol 2006;126:235-240.
Vitale, Antonella et al . Absence of prognostic impact of CD13 and/or CD33 antigen expression in adult acute lymphoblastic leukemia. Results of the GIMEMA ALL 0496 trial. Haematologica, Vol 92, Issue 3, 342-348.