Classification & Risk Stratification Prediction
Overview
If the case disease is Acute Myeloid Leukemia or a subtype, Classification & Risk Stratification Prediction is provided on the Overview Tab.
Classification and risk stratification predictions are based on WHO 2022 and ELN 2022 acute myeloid leukemia guidelines, respectively, focusing on Acute myeloid leukemia with defining genetic abnormalities.
Select a box to review how the evaluation was performed. For more information, refer to Decision Trees below.
Reporting
The report interpretation summary can be generated from the prediction results by clicking Report.
Decision Trees
All variants described below must pass secondary analysis filters (VCF Filter = PASS).
APL with PML::RARA fusion
Classification
Blast count % ≥ 10
History of cytotoxic therapy exposure = No
Any of the following:
Detection of PML::RARA fusion in the Variants Tab
Detection of t(15;17)(q24;q21) in the User Determined Karyotype
If the above is met, the classification is predicted to be APL with PML::RARA fusion.
Risk Stratification
Detection of TP53 variant in the Variants Tab with the following characteristics:
Small variant
Somatic origin (origin = somatic or unknown)
Oncogenic or likely oncogenic (as indicated by a knowledge base biological classification or oncogenicity prediction)
VAF ≥ 0.10 (10%)
If the above is met, the risk stratification is predicted to be Adverse. If not, then Intermediate.
AML with RUNX1::RUNX1T1 fusion
Classification
Blast count % ≥ 10
History of cytotoxic therapy exposure = No
Any of the following:
Detection of RUNX1::RUNX1T1 fusion in the Variants Tab
Detection of t(8;21)(q21.3;q22.1) in the User Determined Karyotype
If the above is met, the classification is predicted to be AML with RUNX1::RUNX1T1 fusion.
Risk Stratification
Detection of TP53 variant in the Variants Tab with the following characteristics:
Small variant
Somatic origin (origin = somatic or unknown)
Oncogenic or likely oncogenic (as indicated by a knowledge base biological classification or oncogenicity prediction)
VAF ≥ 0.10 (10%)
If the above is met, the risk stratification is predicted to be Adverse. If not, then Favorable.
AML with CBFB::MYH11 fusion
Classification
Blast count % ≥ 10
History of cytotoxic therapy exposure = No
Any of the following:
Detection of CBFB::MYH11 fusion in the Variants Tab
Detection of inv(16)(p13.1q22.1) in the User Determined Karyotype
Detection of t(16;16)(p13.1;q22.1) in the User Determined Karyotype
If the above is met, the classification is predicted to be AML with CBFB::MYH11 fusion.
Risk Stratification
Detection of TP53 variant in the Variants Tab with the following characteristics:
Small variant
Somatic origin (origin = somatic or unknown)
Oncogenic or likely oncogenic (as indicated by a knowledge base biological classification or oncogenicity prediction)
VAF ≥ 0.10 (10%)
If the above is met, the risk stratification is predicted to be Adverse. If not, then Favorable.
AML with DEK::NUP214 fusion
Classification
Blast count % ≥ 10
History of cytotoxic therapy exposure = No
Any of the following:
Detection of DEK::NUP214 fusion in the Variants Tab
Detection of t(6;9)(p22.3;q34.1) in the User Determined Karyotype
If the above is met, the classification is predicted to be AML with DEK::NUP214 fusion.
Risk Stratification
Adverse
AML with RBM15::MRTFA fusion
Classification
Blast count % ≥ 10
History of cytotoxic therapy exposure = No
Any of the following:
Detection of RBM15::MRTFA fusion in the Variants Tab
Detection of t(1;22)(p13.3;q13.1) in the User Determined Karyotype
If the above is met, the classification is predicted to be AML with RBM15::MRTFA fusion.
Risk Stratification
Detection of TP53 variant in the Variants Tab with the following characteristics:
Small variant
Somatic origin (origin = somatic or unknown)
Oncogenic or likely oncogenic (as indicated by a knowledge base biological classification or oncogenicity prediction)
VAF ≥ 0.10 (10%)
If the above is met, the risk stratification is predicted to be Adverse. If not, then Intermediate.
AML with BCR::ABL1 fusion
Classification
Blast count % ≥ 20
History of cytotoxic therapy exposure = No
Any of the following:
Detection of BCR::ABL1 fusion in the Variants Tab
Detection of t(9;22)(q34.1;q11.2) in the User Determined Karyotype
If the above is met, the classification is predicted to be AML with BCR::ABL1 fusion.
Risk Stratification
Adverse
AML with KMT2A rearrangement
Classification
Blast count % ≥ 10
History of cytotoxic therapy exposure = No
Detection of KMT2A structural variant in the Variants Tab
If the above is met, the classification is predicted to be AML with KMT2A rearrangement.
Risk Stratification
Detection of TP53 variant in the Variants Tab with the following characteristics:
Small variant
Somatic origin (origin = somatic or unknown)
Oncogenic or likely oncogenic (as indicated by a knowledge base biological classification or oncogenicity prediction)
VAF ≥ 0.10 (10%)
If the above is met, the risk stratification is predicted to be Adverse. If not, then continue below.
Any of the following:
Detection of MLLT3::KMT2A in the Variants Tab
Detection of t(9;11)(p21.3;q23.3) in the User Determined Karyotype
Detection of KMT2A partial tandem duplication in the Variants Tab
If the above is met, the risk stratification is predicted to be Intermediate. If not, then Adverse.
AML with MECOM rearrangement
Classification
Blast count % ≥ 10
History of cytotoxic therapy exposure = No
Any of the following:
Detection of MECOM structural variant in the Variants Tab
Detection of inv(3)(q21.3q26.2) in the User Determined Karyotype
Detection of t(3;3)(q21;q26) in the User Determined Karyotype
Detection of t(3;21)(q26.2;q22) in the User Determined Karyotype
Detection of t(3;12)(q26.2;p13) in the User Determined Karyotype
If the above is met, the classification is predicted to be AML with MECOM rearragement.
Risk Stratification
Adverse
AML with NUP98 rearrangement
Classification
Blast count % ≥ 10
History of cytotoxic therapy exposure = No
Any of the following:
Detection of NUP98 structural variant in the Variants Tab
Detection of t(5;11)(q35.2;p15.4) in the User Determined Karyotype
Detection of t(11;12)(p15.4;p13.3) in the User Determined Karyotype
If the above is met, the classification is predicted to be AML with NUP98 rearrangement.
Risk Stratification
Detection of TP53 variant in the Variants Tab with the following characteristics:
Small variant
Somatic origin (origin = somatic or unknown)
Oncogenic or likely oncogenic (as indicated by a knowledge base biological classification or oncogenicity prediction)
VAF ≥ 0.10 (10%)
If the above is met, the risk stratification is predicted to be Adverse. If not, then Intermediate.
AML with NPM1 mutation
Classification
Blast count % ≥ 10
History of cytotoxic therapy exposure = No
Detection of NPM1 variant in the Variants Tab with the following characteristics:
Small variant
Oncogenic or likely oncogenic (as indicated by a knowledge base biological classification or oncogenicity prediction)
If the above is met, the classification is predicted to be AML with NPM1 mutation.
Risk Stratification
Any of the following:
Detection of TP53 variant in the Variants Tab with the following characteristics:
Small variant
Somatic origin (origin = somatic or unknown)
Oncogenic or likely oncogenic (as indicated by a knowledge base biological classification or oncogenicity prediction)
VAF ≥ 0.10 (10%)
Detection of DEK::NUP214 fusion in the Variants Tab
Detection of t(6;9)(p22.3;q34.1) in the User Determined Karyotype
Detection of KMT2A structural variant without MLLT3 fusion partner in the Variants Tab
Detection of BCR::ABL1 fusion in the Variants Tab
Detection of t(9;22)(q34.1;q11.2) in the User Determined Karyotype
Detection of KAT6A::CREBBP fusion in the Variants Tab
Detection of t(8;16)(p11.2;p13.3) in the User Determined Karyotype
Detection of MECOM structural variant in the Variants Tab
Detection of inv(3)(q21.3q26.2) in the User Determined Karyotype
Detection of t(3;3)(q21;q26) in the User Determined Karyotype
Detection of t(3;21)(q26.2;q22) in the User Determined Karyotype
Detection of t(3;12)(q26.2;p13) in the User Determined Karyotype
Detection of monosomy 5 in the User Determined Karyotype or Variants Tab
Detection of 5q deletion in the User Determined Karyotype, or Variants Tab with length ≥ 5 Mbp
Detection of monosomy 7 in the User Determined Karyotype or Variants Tab
Detection of monosomy 17 in the User Determined Karyotype or Variants Tab
Detection of 17p deletion in the User Determined Karyotype, or Variants Tab with length ≥ 5 Mbp
Detection of complex karyotype in the User Determined Karyotype or Variants Tab
Detection of monosomal karyotype in the User Determined Karyotype or Variants Tab
If the above is met, the risk stratification is predicted to be Adverse. If not, then continue below.
Detection of FLT3 internal tandem duplication in the Variants Tab
If the above is met, the risk stratification is predicted to be Intermediate. If not, then Favorable.
AML with CEBPA mutation
Classification
None of the classifications above should be met.
Blast count % ≥ 20
History of cytotoxic therapy exposure = No
Any of the following:
Detection of 2 CEBPA variants in the Variants Tab with the following characteristics:
Small variant
Oncogenic or likely oncogenic (as indicated by a knowledge base biological classification or oncogenicity prediction)
Detection of CEBPA variant in the Variants Tab with the following characteristics:
Small variant
Oncogenic or likely oncogenic (as indicated by a knowledge base biological classification or oncogenicity prediction)
Located in the bZIP domain
The guideline requires biallelic mutations, whereas the evaluation simply checks for 2 due to lack of cis/trans information.
If the above is met, the classification is predicted to be AML with CEBPA mutation.
Risk Stratification
Detection of TP53 variant in the Variants Tab with the following characteristics:
Small variant
Somatic origin (origin = somatic or unknown)
Oncogenic or likely oncogenic (as indicated by a knowledge base biological classification or oncogenicity prediction)
VAF ≥ 0.10 (10%)
If the above is met, the risk stratification is predicted to be Adverse. If not, then continue below.
Detection of CEBPA variant in the Variants Tab with the following characteristics:
Small variant
Oncogenic or likely oncogenic (as indicated by a knowledge base biological classification or oncogenicity prediction)
In-frame (not a frameshift variant)
If the above is met, the risk stratification is predicted to be Favorable. If not, then Intermediate.
AML with other defined genetic alterations
Classification
None of the classifications above should be met.
Blast count % ≥ 20
History of cytotoxic therapy exposure = No
Any of the following:
Detection of CBFA2T3::GLIS2 fusion in the Variants Tab
Detection of inv(16)(p13q24) in the User Determined Karyotype
Detection of KAT6A::CREBBP fusion in the Variants Tab
Detection of t(8;16)(p11.2;p13.3) in the User Determined Karyotype
Detection of FUS::ERG fusion in the Variants Tab
Detection of t(16;21)(p11;q22) in the User Determined Karyotype
Detection of MNX1::ETV6 fusion in the Variants Tab
Detection of t(7;12)(q36;p13) in the User Determined Karyotype
Detection of NPM1::MLF1 fusion in the Variants Tab
Detection of t(3;5)(q25;q35) in the User Determined Karyotype
If the above is met, the classification is predicted to be AML with other defined genetic alterations.
Risk Stratification
Detection of TP53 variant in the Variants Tab with the following characteristics:
Small variant
Somatic origin (origin = somatic or unknown)
Oncogenic or likely oncogenic (as indicated by a knowledge base biological classification or oncogenicity prediction)
VAF ≥ 0.10 (10%)
If the above is met, the risk stratification is predicted to be Adverse. If not, then continue below.
Any of the following:
Detection of KAT6A::CREBBP fusion in the Variants Tab
Detection of t(8;16)(p11.2;p13.3) in the User Determined Karyotype
If the above is met, the risk stratification is predicted to be Adverse. If not, then Intermediate.
AML, myelodysplasia-related
Classification
None of the classifications above should be met.
Blast count % ≥ 20
History of cytotoxic therapy exposure = No
Any of the following:
History of myelodysplastic syndrome = Yes
Both of the following:
History of myelodysplastic syndrome = Yes
History of myeloproliferative neoplasm = Yes
Detection of complex karyotype in the User Determined Karyotype or Variants Tab
Detection of 5q deletion in the User Determined Karyotype, or Variants Tab with length ≥ 5 Mbp
Detection of monosomy 7 in the User Determined Karyotype or Variants Tab
Detection of 11q deletion in the User Determined Karyotype, or Variants Tab with length ≥ 5 Mbp
Detection of 12p deletion in the User Determined Karyotype, or Variants Tab with length ≥ 5 Mbp
Detection of monosomy 13 in the User Determined Karyotype or Variants Tab
Detection of 17p deletion in the User Determined Karyotype, or Variants Tab with length ≥ 5 Mbp
Detection of isochromosome 17q in the User Determined Karyotype
Detection of idic(X)(q13) in the User Determined Karyotype
Detection of ASXL1 variant in the Variants Tab with the following characteristics:
Small variant
Oncogenic or likely oncogenic (as indicated by a knowledge base biological classification or oncogenicity prediction)
Detection of BCOR variant in the Variants Tab with the following characteristics:
Small variant
Oncogenic or likely oncogenic (as indicated by a knowledge base biological classification or oncogenicity prediction)
Detection of EZH2 variant in the Variants Tab with the following characteristics:
Small variant
Oncogenic or likely oncogenic (as indicated by a knowledge base biological classification or oncogenicity prediction)
Detection of SF3B1 variant in the Variants Tab with the following characteristics:
Small variant
Oncogenic or likely oncogenic (as indicated by a knowledge base biological classification or oncogenicity prediction)
Detection of SRSF2 variant in the Variants Tab with the following characteristics:
Small variant
Oncogenic or likely oncogenic (as indicated by a knowledge base biological classification or oncogenicity prediction)
Detection of STAG2 variant in the Variants Tab with the following characteristics:
Small variant
Oncogenic or likely oncogenic (as indicated by a knowledge base biological classification or oncogenicity prediction)
Detection of U2AF1 variant in the Variants Tab with the following characteristics:
Small variant
Oncogenic or likely oncogenic (as indicated by a knowledge base biological classification or oncogenicity prediction)
Detection of ZRSR2 variant in the Variants Tab with the following characteristics:
Small variant
Oncogenic or likely oncogenic (as indicated by a knowledge base biological classification or oncogenicity prediction)
If the above is met, the classification is predicted to be AML, myelodysplasia-related.
Risk Stratification
Any of the following:
Detection of TP53 variant in the Variants Tab with the following characteristics:
Small variant
Somatic origin (origin = somatic or unknown)
Oncogenic or likely oncogenic (as indicated by a knowledge base biological classification or oncogenicity prediction)
VAF ≥ 0.10 (10%)
Detection of monosomy 5 in the User Determined Karyotype or Variants Tab
Detection of 5q deletion in the User Determined Karyotype, or Variants Tab with length ≥ 5 Mbp
Detection of monosomy 7 in the User Determined Karyotype or Variants Tab
Detection of monosomy 17 in the User Determined Karyotype or Variants Tab
Detection of 17p deletion in the User Determined Karyotype, or Variants Tab with length ≥ 5 Mbp
Detection of complex karyotype in the User Determined Karyotype or Variants Tab
Detection of monosomal karyotype in the User Determined Karyotype or Variants Tab
Detection of ASXL1 variant in the Variants Tab with the following characteristics:
Small variant
Oncogenic or likely oncogenic (as indicated by a knowledge base biological classification or oncogenicity prediction)
Detection of BCOR variant in the Variants Tab with the following characteristics:
Small variant
Oncogenic or likely oncogenic (as indicated by a knowledge base biological classification or oncogenicity prediction)
Detection of EZH2 variant in the Variants Tab with the following characteristics:
Small variant
Oncogenic or likely oncogenic (as indicated by a knowledge base biological classification or oncogenicity prediction)
Detection of SF3B1 variant in the Variants Tab with the following characteristics:
Small variant
Oncogenic or likely oncogenic (as indicated by a knowledge base biological classification or oncogenicity prediction)
Detection of SRSF2 variant in the Variants Tab with the following characteristics:
Small variant
Oncogenic or likely oncogenic (as indicated by a knowledge base biological classification or oncogenicity prediction)
Detection of STAG2 variant in the Variants Tab with the following characteristics:
Small variant
Oncogenic or likely oncogenic (as indicated by a knowledge base biological classification or oncogenicity prediction)
Detection of U2AF1 variant in the Variants Tab with the following characteristics:
Small variant
Oncogenic or likely oncogenic (as indicated by a knowledge base biological classification or oncogenicity prediction)
Detection of ZRSR2 variant in the Variants Tab with the following characteristics:
Small variant
Oncogenic or likely oncogenic (as indicated by a knowledge base biological classification or oncogenicity prediction)
If the above is met, the risk stratification is predicted to be Adverse. If not, then Intermediate.
Definitions
Complex Karyotype
According to WHO/ISCN: ≥ 3 abnormalities, where abnormalities are counted as follows:
Only clonal abnormalities are counted; abnormalities present in only 1 metaphase are ignored.
Numerical gains and losses, simple and complex balanced translocations, unbalanced aberrations involving one chromosome, as well as multiplication of a complete chromosome set are counted as one abnormality.
Unbalanced aberrations involving two or more chromosomes, tetrasomy of same chromosome, triplication or quadruplication, as well as isoderivative chromosomes, are counted as 2 abnormalities.
Constitutional abnormalities are not counted.
In case of multiple clones (subclones or independent clones), chromosome abnormalities in each clone/subclone are counted separately and the number of chromosomal abnormalities is defined by the clone with the highest abnormalities.
For composite karyotypes, clonal chromosomal aberrations are counted in metaphases with the highest number of abnormalities.
Monosomal Karyotype
According to ELN: Presence of two or more distinct monosomies (excluding loss of X or Y), or one single autosomal monosomy in combination with at least one structural chromosome abnormality.
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