Molecular Boards: Hematopathology

Front 1

What does the FLT3 gene do?

B: what are the common mutations?

C: how is it tested?

Back 1

A: It is a tyrosine kinase. Mutations lead to unstoppable activation of the pathway

B: MC, short duplications- internal tandem duplication (ITD) that changes the length of the protein at the juxtamembrane region (30% of AMLs). Rarely there are mutations in the activation loop.

C: at barnes- STR for ITD, genotype/ hybridization assay for activation loop mutations.

Front 2

What are major pre-treatment predictors of poor outcome in AML?

1.
2.
3.

Back 2

pre-treatment predictors of poor outcome in AML

1. Abnormal karyotype
2. FLT3 mutation
3. Old age

Front 3

What are 3 karyotypes that signify a favorable risk group in AML?

1.
2.
3.

Back 3

Favorable risk in AML

1. t(8;21)
2. t(15;17)
3. inv (16) , t(16;16)

Front 4

Rearrangements in what two gene classes result in ALL?

How are these tested?

Back 4

1. IG
2. TCR

Both are responsible for genetic diversity of the antigen-specific lymphocyte receptors at the V, D, and L loci. Rearrangements at these loci is normal. In ALL, there is cross- rearrangement from a region outside of these loci.

B: sequencing the V, D, and J regions with primers that hybridize to conserved regions. Multiple primers must be used since rearrangements will only yield products in unpredictable ways in 3 loci.

Front 5

What is the most common rearrangement seen in childhood ALL?

Back 5

t(1;19)(q23;p13) in about 25% of cases. BCR-ABL t(9;22) is seen in ~5% of cases, although it is more frequent in adults.

Front 6

How is clonality assessed in B-Cell lymphomas?

T-Cell lymphomas?

Back 6

PCR if IGH regions (V,J,D), with capillary electrophoresis. There should be multiple peaks. If only 1, then there is a clone.

Similar, with TCR genes instead of IGH.