Table 1.

Genetic alterations of diagnostic use and/or therapeutic or prognostic value in routine clinical practice in select myeloid neoplasms

Disease subtype*Genes†Frequency, %Normal functionTechnology used to detectPrognostic marker‡Genotype-directed therapies
AML t(8;21)(q22;q22.1); RUNX1-RUNX1T1 7 RUNX1 and CBFB are core-binding factor transcription factors Karyotype, FISH Favorable  
inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11 5 Karyotype, FISH Favorable  
PML-RARA 13 Retinoic acid receptor FISH, PCR Favorable ATRA, Arsenic 
t(9;11)(p21.3;q23.3);
MLLT3-KMT2A 		4 Histone methyltransferase    
t(6;9)(p23;q34.1); DEK-NUP214 1 Nucleoporin (NUP214)  Adverse  
inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2, MECOM 1 Transcription factor  Adverse  
t(1;22)(p13.3;q13.3);
RBM15-MKL1 		<1 RNA-binding protein (RBM15) and transcription factor (MKL1)    
NPM1 29 Nucleolar phosphoprotein Sequencing Favorable MRD monitoring 
FLT3-ITD, TKD 37 Receptor tyrosine kinase Sequencing, PCR Adverse FLT3 inhibitors 
Biallelic CEBPA 9 Transcription factor Sequencing Favorable  
RUNX1 10 Transcription factor Sequencing Adverse  
AML with BCR-ABL1 1 Tyrosine kinase  Adverse TKIs 
IDH1/2 15-20 α-KG hydroxylase in TCA cycle Sequencing  Trials involving mutant IDH1/2 inhibitors 
MLL-PTD, rearranged 5 Histone methyltransferase FISH, PCR, sequencing Adverse (in selected cases)  
Chromatin† 13 Epigenetic regulation Sequencing Adverse  
Spliceosome† 5 Pre-mRNA splicing Sequencing Adverse Trials involving splicing inhibitors 
TP53 2 Tumor suppressor Sequencing Adverse  
KIT 5 Tyrosine kinase Sequencing  TKIs 
MDS SF3B1 15-30 Pre-mRNA splicing Sequencing Favorable Trials involving splicing inhibitors 
Del5q 6 Multiple genes Karyotype Favorable Lenalidomide 
ASXL1 15-20 Epigenetic regulation Sequencing Adverse  
MPNs       
 BCR-ABL1+ BCR-ABL1 ∼100 Tyrosine kinase FISH, PCR  TKIs 
 Non-BCR-ABL1 SETBP1  Multiple roles Sequencing   
JAK2 74 Tyrosine kinase Sequencing, PCR   
CALR 17 Endoplasmic reticulum Sequencing, PCR Favorable  
MPL 3 Thrombopoietin receptor Sequencing   
ASXL1 7-25 Epigenetic regulation Sequencing Adverse  
CSF3R 100 G-CSF receptor Sequencing  Ruxolitinib 
MDS/MPN       
 CMML TET2 61 DNA hydroxymethylation Sequencing   
SRSF2 47 Pre-mRNA splicing Sequencing  Trials involving splicing inhibitors 
ASXL1 44 Epigenetic regulation Sequencing Adverse  
 MDS/MPN-RS-T SF3B1 67 Pre-mRNA splicing Sequencing  Trials involving splicing inhibitors 
JAK2 44 Tyrosine kinase Sequencing, PCR   
Mastocytosis KIT 81 Tyrosine kinase Sequencing  TKIs 
Disease subtype*Genes†Frequency, %Normal functionTechnology used to detectPrognostic marker‡Genotype-directed therapies
AML t(8;21)(q22;q22.1); RUNX1-RUNX1T1 7 RUNX1 and CBFB are core-binding factor transcription factors Karyotype, FISH Favorable  
inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11 5 Karyotype, FISH Favorable  
PML-RARA 13 Retinoic acid receptor FISH, PCR Favorable ATRA, Arsenic 
t(9;11)(p21.3;q23.3);
MLLT3-KMT2A 		4 Histone methyltransferase    
t(6;9)(p23;q34.1); DEK-NUP214 1 Nucleoporin (NUP214)  Adverse  
inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2, MECOM 1 Transcription factor  Adverse  
t(1;22)(p13.3;q13.3);
RBM15-MKL1 		<1 RNA-binding protein (RBM15) and transcription factor (MKL1)    
NPM1 29 Nucleolar phosphoprotein Sequencing Favorable MRD monitoring 
FLT3-ITD, TKD 37 Receptor tyrosine kinase Sequencing, PCR Adverse FLT3 inhibitors 
Biallelic CEBPA 9 Transcription factor Sequencing Favorable  
RUNX1 10 Transcription factor Sequencing Adverse  
AML with BCR-ABL1 1 Tyrosine kinase  Adverse TKIs 
IDH1/2 15-20 α-KG hydroxylase in TCA cycle Sequencing  Trials involving mutant IDH1/2 inhibitors 
MLL-PTD, rearranged 5 Histone methyltransferase FISH, PCR, sequencing Adverse (in selected cases)  
Chromatin† 13 Epigenetic regulation Sequencing Adverse  
Spliceosome† 5 Pre-mRNA splicing Sequencing Adverse Trials involving splicing inhibitors 
TP53 2 Tumor suppressor Sequencing Adverse  
KIT 5 Tyrosine kinase Sequencing  TKIs 
MDS SF3B1 15-30 Pre-mRNA splicing Sequencing Favorable Trials involving splicing inhibitors 
Del5q 6 Multiple genes Karyotype Favorable Lenalidomide 
ASXL1 15-20 Epigenetic regulation Sequencing Adverse  
MPNs       
 BCR-ABL1+ BCR-ABL1 ∼100 Tyrosine kinase FISH, PCR  TKIs 
 Non-BCR-ABL1 SETBP1  Multiple roles Sequencing   
JAK2 74 Tyrosine kinase Sequencing, PCR   
CALR 17 Endoplasmic reticulum Sequencing, PCR Favorable  
MPL 3 Thrombopoietin receptor Sequencing   
ASXL1 7-25 Epigenetic regulation Sequencing Adverse  
CSF3R 100 G-CSF receptor Sequencing  Ruxolitinib 
MDS/MPN       
 CMML TET2 61 DNA hydroxymethylation Sequencing   
SRSF2 47 Pre-mRNA splicing Sequencing  Trials involving splicing inhibitors 
ASXL1 44 Epigenetic regulation Sequencing Adverse  
 MDS/MPN-RS-T SF3B1 67 Pre-mRNA splicing Sequencing  Trials involving splicing inhibitors 
JAK2 44 Tyrosine kinase Sequencing, PCR   
Mastocytosis KIT 81 Tyrosine kinase Sequencing  TKIs 

AML, acute myeloid leukemia; ATRA, all-trans retinoic acid; CBFB, core-binding factor-β subunit; CML, chronic myelogenous leukemia; CMML, chronic myelomonocytic leukemia; FISH, fluorescence in situ hybridization; G-CSF, granulocyte–colony-stimulating factor; IDH, isocitrate dehydrogenase; MDS, myelodysplastic syndrome; MDS/MPN, myelodysplastic syndrome/myeloproliferative neoplasm; MDS/MPN-RS-T, myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis; MRD, minimal residual disease; mRNA, messenger RNA; PCR, polymerase chain reaction; TCA cycle, tricarboxylic acid cycle; TKI, tyrosine kinase inhibitor.

*

Gene/cytogenetic names in bold are of diagnostic value.

†

Genes mutated in this category are defined by Döhner et al1  and Papaemmanuil et al.8 

‡

Those genes left blank do not have clear prognostic relevance currently.

View Large
Close Modal
This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal