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Leukemia - Acute

AML with recurrent genetic abnormalities

AML with t(8;21)(q22;q22) - RUNX1-RUNX1T1


Reviewer: Syed Zaidi, M.D. (see Reviewers page)
Revised: 30 December 2011, last major update December 2011
Copyright: (c) 2001-2011, PathologyOutlines.com, Inc.

Definition
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● Translocation produces fusion product of RUNX1T1 (ETO) gene on #8q22 and RUNX1 gene on #21q22
● ~ 5% of AML, and 10% of cases of AML-M2 (AML with maturation) in FAB classification
● Most common type of childhood AML
● RUNX1-RUNX1T1 may facilitate accumulation of genetic alterations by suppressing endogenous DNA repair (Blood 2008;111:2190)
● Additional mutations are required for leukemogenesis (Proc Natl Acad Sci USA 2000;97:7521)
● Frequently associated with additional chromosomal translocations which may influence prognosis (Zhonghua Nei Ke Za Zhi 2006;45:918)
● Classify as AML even if initial blast count is < 20%
● RT-PCR and cytogenetics for detection both have limitations (J Clin Oncol 2001;19:2482)
Variant t(8;21): similar clinical features, morphology and immunostaining as classic t(8;21) cases (Am J Clin Pathol 2006;125:267)

Prognostic features
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● Favorable prognosis in adults, although KIT activating mutations confer poorer prognosis
● Good response to chemotherapy and high complete remission rate
● Expression of CD56 and KIT mutations are considered adverse prognostic factors

Case reports
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● With occult mastocytosis (J Clin Pathol 2004;57:324)

Micro description
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● Resembles AML-M2 (AML with maturation) - large blasts, abundant basophilic cytoplasm, frequent large Auer rods and chunky cytoplasmic granules, perinuclear hofs, neutrophil dysplasia
● Trilineage dysplasia present in therapy related cases (Am J Clin Pathol 2002;117:306)
● Peripheral blood contains smaller blasts

Micro images
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Bone marrow smear (Wright-Giemsa):

Myelocytes have abundant cytoplasm with prominent granulation, one myeloblast (slightly left and below center) has prominent Auer rod


Myeloblasts with Auer rods, promyelocytes and other mature cells


Large blast cells with abundant basophilic cytoplasm, often numerous azurophilic granules, may have large granules (pseudo Chediak-Higashi granules), often Auer rods, accompanied by promyelocytes, myelocytes and mature granulocytes with variable dysplasia


H&E and stains

Positive stains
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● CD19 (75-93%) and CD56 in fraction of cases (and may have adverse prognostic significance), aberrant expression compared to classic AML M2 (Am J Clin Pathol 2007;128:550)
● Also PAX5/BSAP (usually weak), OCT2 (75%, Am J Clin Pathol 2006;126:235)
● High levels of CD34 and myeloperoxidase and low levels of CD33 by flow cytometry (Mod Pathol 2004;17:1211)

Negative stains
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● CD20, CD22, CD79a

Molecular / cytogenetics description
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● t(8;21)(q22;q22), RUNX1-RUNX1T1 AML1 gene also called RUNX1, encodes core binding factor alpha

Molecular / cytogenetics images
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t(8;21) with abnormal chromosomes on right, and breakpoints at arrowheads

Various images

Variants

End of Leukemia - Acute > AML with recurrent genetic abnormalities > AML with t(8;21)(q22;q22) - RUNX1-RUNX1T1


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