This Chromosomal Microarray Analysis (CMA) assay detects DNA copy number gains and losses as well as regions of loss of heterozygosity (LOH) by SNP analysis. It is particularly useful as a more comprehensive replacement of FISH panels for myelodysplastic syndrome (MDS) and chronic lymphocytic leukemia (CLL), as millions of oligonucleotide probes across the genome are interrogated for gains and losses, and copy-neutral LOH is detected as well. Approximately half of patients with known MDS have a normal karyotype, and the microarray has a greater diagnostic yield than FISH panels. The CMA assay is particularly useful for malignant conditions with a low mitotic index and when limited material is available for cell culture for karyotypes. This assay is also useful in the detection of clonal abnormalities to help establish a diagnosis of MDS.

Bone marrow aspirate specimens with at least 20% involvement by malignant cells are most useful for the evaluation of acute leukemia, MDS, or myeloproliferative neoplasia. Contact the laboratory to verify suitability of peripheral blood.

CLL has prognostically significant gains and losses that are difficult to detect by karyotype due to lack of mitotic activity in cell culture. FISH panels have been more informative, however, the higher resolution of a genomic microarray and the detection of LOH by SNPs provide a comprehensive overview of genetic complexity and aberrations involving clinically important loci. For example, LOH of 17p is often correlated with homozygous mutations of the TP53 locus, which are associated with a worse prognosis.

For CLL, peripheral blood specimens obtained at the time of diagnosis or with high levels of recurrent/residual leukemia are most suitable. For post-therapy testing for evolution, FISH for p53 (TP53 locus) or the CLL FISH panel is recommended. As the CMA assay does not detect balanced chromosome abnormalities, FISH analysis for the t(11;14) associated with mantle cell lymphoma should be ordered separately, if indicated (see FISH for Malignancy, or FISH for CLL Handbook listings).

Acute lymphoblastic leukemia (ALL) at diagnosis may have clinically important copy number changes revealed by microarray with SNPs. ALL karyotypes are frequently normal even when FISH demonstrates clonal abnormalities, due to the poor morphology of ALL and the resulting difficulty in obtaining analyzable metaphase cells. Many genetic abnormalities detected at diagnosis have prognostic significance and can be used to monitor response to therapy. Furthermore, sub-microscopic deletions with prognostic significance have been identified by oligonucleotide and SNP arrays; for example, IKZF1 gene deletions are associated with a poor prognosis. CDKN2A/B deletions are common, and LOH for 9p is associated with homozygous mutations of CDKN2A.

For ALL, note that clinically important balanced rearrangements would not be detected; thus, the CCA assay is complementary to the standard karyotype. Also, at least 20% blasts must be present in a peripheral blood sample, if submitted.