Interpretive Handbook

Acute myeloid leukemia (AML) is one of the most common adult leukemias, with almost 10,000 new cases diagnosed per year. AML also comprises 15% of pediatric acute leukemia and accounts for the majority of infant (<1 year old) leukemia. Several subtypes of AML have been recognized (termed AML-M0, M1, M2, M3, M4, M5, M6, and M7) based on the cell morphology and myeloid lineage involved.

In addition to morphology, several recurrent chromosomal abnormalities have been linked to specific subtypes of AML. The most common chromosome abnormalities associated with AML include t(8;21), t(15;17), inv(16), +8, t(6;9), t(8:16), t(1;22), t(9;22) and abnormalities of the MLL gene at 11q23. The most common genes juxtaposed with MLL through translocation events in AML include MLTT4- t(6;11), MLLT3- t(9;11), MLLT10- t(10;11), CREBBP- t(11;16), ELL- t(11;19p13.1), and MLLT1-t(11;19p13.3).

AML can also evolve from myelodysplasia (MDS). Thus, the common chromosome abnormalities associated with MDS can also be identified in AML, which include: inv(3), -5/5q-, -7/7q-, +8, 13q-, 17p-, 20q-, t(1;3), and t(3;21).

In combination, the multiple recurrent chromosome abnormalities identified in patients with AML are observed in approximately 60% of diagnostic AML cases.

Conventional chromosome analysis is the gold standard for identification of the common, recurrent chromosome abnormalities in AML. However, this analysis requires dividing cells, takes 5 to 7 days to process, and some of the subtle rearrangements can be missed (eg, inv[16] and MLL anomalies). Thus, we have validated a combination of commercially available and Mayo in-house developed FISH probes to detect the common chromosome abnormalities observed in AML patients. These probes have diagnostic and prognostic relevance and can also be used to track response to therapy.

Our panel of multiple FISH probes can be utilized to study nonproliferating (interphase) cells and can identify the all the common cytogenetic abnormalities associated with AML.

Detecting a neoplastic clone associated with the common chromosome anomalies seen in patients with acute myeloid leukemia or other myeloid malignancies

Evaluating specimens in which standard cytogenetic analysis is unsuccessful

Identifying and tracking known chromosome anomalies in patients with myeloid malignancies and tracking response to therapy

A neoplastic clone is detected when the percent of cells with an abnormality exceeds the normal reference range for any given probe.

Detection of an abnormal clone likely indicates a diagnosis of an acute myeloid leukemia of various subtypes.

The absence of an abnormal clone does not rule out the presence of a neoplastic disorder.

This test is not approved by the FDA and it is best used as an adjunct to existing clinical and pathologic information.

An interpretive report will be provided.

1. Grimwade D, Hills RK, Moorman AV, et al: Refinement of cytogenetics classification in acute myeloid leukemia: determination of prognostic significance or rare recurring chromosomal abnormalities among 5879 younger adult patients treated in the United Kingdom Research Council trials. Blood 2010 Jul;116(3):354-365

2. International Agency for Research on Cancer (IARC): World Health Organization (WHO) classification of tumour of haematopoietic and lymphoid tissues. Edited by SH Swerdlow, E Campo, NL Harris, et al. IARC Press, Oxford: Oxford University Press (distributor), 2008