Bone Marrow Aspirate
Formalin fixed, paraffin-embedded tissue

2 mL bone marrow aspirate. Specimens for which the AML blast count is at least 20% will be tested. Testing on specimens with a lower blast count may be attempted with approval of lab director. However, such testing is not recommended due to the increased possibility of a false- negative result.

Blast count less than 20%, hemolyzed, green top, decalcified bone marrow.

Testing is generally not available on a STAT basis. However, expedited testing can be arranged by contacting the Molecular Pathology Laboratory at 384-9568 or the Molecular Genetic Pathology Fellow (pager #8682).

Weekly

7-10 working days

Unaffected samples will lack disease-associated CEBPA mutations, but may harbor previously identified single nucleotide polymorphisms (SNPs) that are reported as incidental findings.

In the bone marrow, the CCAAT/enhancer-binding protein, alpha (CEBPA) is a myelomonocytic lineage-specific transcription factor that promotes myeloid differentiation (1). Mutations in the CEBPA gene have been reported in acute myelogenous leukemia (AML; 5-14% of cases) and myelodysplastic syndromes (2-7). In the absence of other genetic lesions known to confer a poor prognosis (e.g., FLT3-ITD mutation), mutations in CEBPA are associated with a favorable prognosis for AML. However, the benefit appears to be restricted to cases in which there are biallelic CEBPA mutations, often consisting of two discrete (compound heterozygous) mutations affecting different functional domains of the CEBPA protein (3-5). A variety of inactivating point mutations, deletions and insertions have been described, requiring evaluation of the entire CEBPA coding sequence.

References
1. Zhang P, et al. Immunity 2004;21(6):853-63.
2. Nerlov C. Nature Reviews Cancer 2004;4(5):394-400.
3. Dufour A, et al. J Clin Oncol 2010;28(4):570-7.
4. Wouters BJ, et al. Blood 2009;113(13):3088-91.
5. Taskesan E, et al. Blood 2011;117:2469-75.
6. Gombart AF, et al. Blood 2002;99(4):1332-1340.
7. Shih LY, et al. Clin Cancer Res 2005;11(5):1821-26.

20% mutant allele

PCR amplification of CEBPA-specific fragments followed by DNA cycle sequencing (Sanger method).

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