Leukemia - Acute
Recurrent genetic abnormalities
AML with inv(16)(p13.1;q22) or t(16;16)(p13.1;q22); CBFB-MYH11

Author: Syed Zaidi, M.D. (see Authors page)

Revised: 29 March 2018, last major update May 2014

Copyright: (c) 2001-2018, PathologyOutlines.com, Inc.

PubMed Search: AML with inv(16)(p13.1;q22)

Cite this page: Zaidi, S. AML with inv(16)(p13.1;q22) or t(16;16)(p13.1;q22); CBFB-MYH11. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/leukemiainv16.html. Accessed August 16th, 2018.
Definition / general
  • 5 - 8% of all cases of adult AML
  • Associated with more frequent hepatosplenomegaly, lymphadenopathy and granulocytic sarcoma than AML in general
  • Longer median survival than other AML (Am J Clin Pathol 2003;119:672); when treated with high dose cytarabine in consolidation phase, complete remission rates are 76% - 92%
  • If translocation present, consider as AML even if initial blast count is < 20%
  • FISH recommended if suggestive cell morphology, but negative cytogenetics (J Mol Diagn 2004;6:271)
  • Poor prognostic factors: high initial white blood cell count (for complete response); age > 35 years (for disease free survival, Blood 2003;102:462); older patients with KIT mutation for higher risk of relapse
  • Peripheral blood: monocytosis, high blast count
Microscopic (histologic) description
  • Usually features of AML M4 (acute myelomonocytic leukemia) plus marrow eosinophilia, with dysplastic eosinophils containing large basophilic staining granules, especially in promyelocyte and myelocyte stages, less evident at later stages of eosinophil maturation (Am J Clin Pathol 2003;120:236)
  • Granules are large, purple-violet, may obscure cell morphology
  • Few mature abnormal eosinophils show faint staining with naphthol ASD chloroacetate esterase (negative in normal eosinophils); blasts have few Auer rods
Microscopic (histologic) images

Bone marrow smears (Wright-Giemsa):

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Eosinophil precursors
show prominent
basophilic staining
granules



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Eosinophil precursors
show prominent
basophilic staining
granules

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H&E, RT-PCR and FISH

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Immature cells with folded monocytoid nuclei
mixed with abnormal eosinophils (arrow),
containing large basophilic granules
and more normal eosinophil granules

Positive stains
Molecular / cytogenetics description
  • Inversion(16) much more common than t(16;16)(p13;q22), but both cause fusion of CBFβ to MYH11
  • Smooth muscle myosin heavy chain gene (SMMHC) produces MYH11 at 16p13.1; core binding factor beta (CBF-β) gene produces CBFβ at 16q22; fusion gene is CBFβ - MYH11 protein (Science 1993;261:1041, Proc Natl Acad Sci USA 1998;95:11863)
  • May need FISH and RT-PCR to document the genetic alteration, because the rearrangement is subtle and easily overlooked in metaphase preparation
  • Trisomy 22 is fairly specific for inv(16); mutations of KIT are seen in 30% of patients
  • Multiple fusion transcripts exist (J Mol Diagn 2004;6:22); fusion transcripts appear to upregulate NF-kappaB signaling pathway (Mod Pathol 2007;20:811)
Molecular / cytogenetics images

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Two G banded chromosomes,
show pericentric inversion at #16,
arrowheads point to breakpoints
on abnormal chromosome



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Diagram

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Contributed by Dr. Nikhil Sangle, University of Utah Health Sciences Center