What is the human genetic mark

Genetic markers

Acute myeloid leukemia (AML) is a heterogeneous group of diseases within which biologically and prognostically different subgroups can be distinguished. The karyotype is one of the most important independent prognostic factors.

Karyotype

The karyotype of the leukemic blasts is the most important independent prognostic parameter with regard to both response to therapy and survival. About 40-45% of AML cases have a normal karyotype. Balanced or unbalanced chromosome changes can be detected in over 50% of adult patients. With the help of cytogenetics, it has been possible to describe more than 50 recurring chromosome aberrations based on the criteria of the Medical Research Council (MRC) can be divided into three prognostic groups [1] (frequency [2]).

forecast

Chromosome aberration

Fusion gene

frequency

Cheap

t (15; 17) (q22; q21)

PML-RARA

5-10 %

 

t (8; 21) (q22; q22)

RUNX1-RUNX1T1

10-15 %

 

inv (16) (p13q22) / t (16; 16) (p13; q22)

CBFB-MYH11

3-8 %

Intermediary

Entities that are neither favorable nor unfavorable

   

Unfavorable

ab (3q) [excluded t (3; 5) (q21∼25; q31∼35)]

   
 

inv (3) (q21q26) / t (3; 3) (q21; q26),

   
 

add (5q), del (5q), −5

   
 

−7, add (7q) / del (7q)

   
 

t (6; 11) (q27; q23)

MLL-MLLT4

5-9% (total MLL fusion)

 

t (10; 11) (p11∼13; q23)

MLL-MLLT10

 
 

t (11q23) [excluded t (9; 11) (p21∼22; q23) and t (11; 19) (q23; p13)]

   
 

t (9; 22) (q34; q11)

BCR OJ

 
 

−17 / ab (17p)

   
 

Complex (≥ 4 unrelated cytogenetic changes)

   

Gene mutations

In addition to the karyotype, molecular aberrations also play an important role in the diagnosis and prognosis of AML. The most common mutations are listed below (frequency, prognosis [2]).

mutation

frequency

forecast

NPM1

25-35 %

Cheap

FLT3-ITD

20-28 %

unfavorable

FLT3-TKD

5-10 %

 

NRAS

9-14 %

 

KRAS

5-17 %

 

CEBPA

10-20 %

Cheap

MLL-PTD

5-13 %

 

RUNX1

5-13 %

 

IDH1 / 2

15-21 %

cheap (IDH2)

TET2

8-27 %

unfavorable

TP53

7-12 %

unfavorable

CBL

2-3 %

 

ITD: internal tandem duplication; TKD: tyrosine kinase domain; PTD: partial tandem duplication.

References and sources

  1. Grimwade D, Hills RK, Moorman AV, Walker H, Chatters S, Goldstone AH, Wheatley K, Harrison CJ, Burnett AK. National Cancer Research Institute AdultLeukemia Working Group. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood. 2010; 116 (3): 354-65. PMID: 20385793. doi: 10.1182 / blood-2009-11-254441.
  2. Naoe T, Kiyoi H. Gene mutations of acute myeloid leukemia in the genome era. Int J Hematol. 2013; 97 (2): 165-74. PMID: 23359299. doi: 10.1007 / s12185-013-1257-4.

Created by: Hehn (Information Center) on September 17, 2014, last change: October 5, 2015