Page 402 - Clinical Hematology_ Theory _ Procedures ( PDFDrive )

386 PART 6 ■ Neoplastic Disorders

C m
Frequency of Recurrent Gene
TABLE 21.4 mm
Mutations in Adults w ith AML
(DNM 3A, ASXL1, IDH2, E 2) -

Mutation % Frequency k m m m -
AML. A k m m

NPM1 25–35 m x m -

CEBPA 6–10 , . C m
m m
RUNX1 5–15
k m
FLT3-ITD ±20 m . M m

NRAS ±15 AML — m -

DNMT3A 18–22 m m -

m . C m
ASXL1 5–17
AML -
TET2 7–25 m AML. NPM1AML k m

Modi ed from Döhner H, Weisdorf DJ, Bloom eld CD. Acute myeloid leu- AML .

kemia, N Engl J Med, 12(373):1140, 2015. NPM m m

.

m m m

k k m WHO Classi cation Revisions

. A x m - T WHO (B x . )

- m x,

- (A RA). A RA m m FAB AML

( ; ) AML (B x . )

m k m . (B x . ).

NOTE: This is a good time to review questions related to the Genetic Differences

preceding content.
A AML m mm m -

, m m
Molecular Analysis k m -

. I m m m
NGS m AML , m j AML

q m ( . . ) m ,

. NGS

m q x k m ■ FL 3 (Fm - k k )

m . ■ C - (CBF) m x

TABLE 21.5 Eight Functional Categories of Genes Commonly Mutated in Acute Myeloid Leukemia

Functional Category Mutations Examples of Mutated Genes

1. Class III signaling genes Tyrosine kinase receptor gene (FLT3)

2. Myeloid transcription factors RUNX1

3. Nucleocytoplasmic shuttling protein Nucleophosmin (NPM1)

4. Spliceosome-complex genes for regulation of RNA processing splicing SRSF 2

5. Cohesin-complex genes for accurate chromosome segregation and transcriptional STAG 2

regulation

6. Chromatin modi cation regulation ASXL1

7. DNA methylation TET 2

8. Myeloid transcriptional regulations TP53 (a tumor suppressor gene)

Modi ed from The Cancer Genome Atlas Research Network. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia, N Engl J Med,

368:2059–2074, 2013.