Case 6: AML with Inversion 16

Inversion of chromosome 16 is associated with acute myeloid leukemia with abnormal eosinophils

These abnormal eosinophils have mixed eosinophilic and basophilic granules

How is the cytogenetic abnormality determined diagnostically?

A brief introduction to cytogenetics…

Cytogenetics is the microscopic investigation of the DNA structure/content at the chromosomal level using banding of metaphase preparations

Banding = darker and lighter areas on a chromosome, which are reproducible across specimens

Most common type of banding is G-banding:

• Dark bands: AT-rich, heterochromatic, fewer active genes
• Light bands: CG-rich, euchromatic, more active genes

From Wikipedia ⬇️

Our talented technologists identify banded chromosomes by assessing (in order):

1. Chromosome size
2. Centromere position
3. Banding pattern

From ASH and Wikipedia ⬇️

Cytogenetics studies are essential in making a diagnosis of AML with inv 16

This can be subtle on conventional karyotype, so further testing with FISH/molecular is warranted if the karyotype is normal but the morphology suggests inv 16

From PEIR @UABPathology ⬇️

Molecular Pathogenesis

The inversion of chromosome 16 (or the translocation t(16;16) leads to the fusion of CBF-beta and MYH11.

CBF normally binds to enhancers/promoters of genes involved in hematopoiesis, increasing transcription of these target genes, leading to hematopoietic differentiation/maturation

With the fusion gene, this process is blocked ➡️ less transcription of target genes ➡️ less hematopoietic differentiation/maturation ➡️ disease

Finally, it's important to note that AML with inversion 16 is considered to be in the favorable risk category

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