Figure 1.
The pathogenic and likely pathogenic germline variants identified in 391 AML patients. (A) The percentage frequency of patients with pathogenic and likely pathogenic (P/LP) and variants of uncertain significance (VUS) in 391 patients. For patients 4039 and 2664, each has 2 germline variants, 1 in each P and LP category and thus counted once only in P category. (B) The percentage frequency of P and LP variants associated with gene strength for 50 unique variants. To define gene strength, 291 genes were selected for curation based on a comprehensive literature review. The strength of the genes is assigned from 1 to 5, depending on the evidence supporting their association with cancer predisposition to either hematological malignancies or other types of cancer, inherited hematological disorders that may predispose to hematological neoplasms, or reported as a somatic variant contributing to the pathogenesis of hematological malignancies. (C) Number of pathogenic and likely pathogenic germline variants in 34 genes for 56 variants in 53 patients, categorized by the gene strength. Variants in genes with “$” were associated with autosomal dominant conditions and those with asterisks were associated with AR syndromes. (D) Percentage frequency of variants classified by type of variants for 50 unique P/LP variants. (E-F) Association of P and LP variants with disease specific subgroups (E) or 2017 ELN risk categories (F) based on available information for 52 and 40 patients, respectively, compared with the whole cohort recruitment for those categories. P and LP variants identified in tier 1 genes only are shown on the right side. (G-H) Percentage frequency of P and LP variants classified by gender and age where denominator is the number of samples in that particular group within 391 patients. A subset of patients with germline P and LP variants identified in the tier 1 genes is presented in the graphs on the right. (I) Genes harboring number of P and LP variants in each of 3 age groups. ** indicates P value <.01. AEL, acute erythroid leukemia; AML NOS, acute myeloid leukemia, NOS; AML NPM1mut, AML with mutated NPM1; AML with CBFB-MYH11, AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11; AML with KMT2A-MLLT3, AML with t(9;11)(p22;q23); KMT2A-MLLT3; AML with RPN1-EVI1, AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1; AML-MRC, AML with myelodysplasia-related changes; AMML, acute myelomonocytic leukemia; AMoL, acute monoblastic and monocytic leukemia; tMNs, therapy-related myeloid neoplasms.

The pathogenic and likely pathogenic germline variants identified in 391 AML patients. (A) The percentage frequency of patients with pathogenic and likely pathogenic (P/LP) and variants of uncertain significance (VUS) in 391 patients. For patients 4039 and 2664, each has 2 germline variants, 1 in each P and LP category and thus counted once only in P category. (B) The percentage frequency of P and LP variants associated with gene strength for 50 unique variants. To define gene strength, 291 genes were selected for curation based on a comprehensive literature review. The strength of the genes is assigned from 1 to 5, depending on the evidence supporting their association with cancer predisposition to either hematological malignancies or other types of cancer, inherited hematological disorders that may predispose to hematological neoplasms, or reported as a somatic variant contributing to the pathogenesis of hematological malignancies. (C) Number of pathogenic and likely pathogenic germline variants in 34 genes for 56 variants in 53 patients, categorized by the gene strength. Variants in genes with “$” were associated with autosomal dominant conditions and those with asterisks were associated with AR syndromes. (D) Percentage frequency of variants classified by type of variants for 50 unique P/LP variants. (E-F) Association of P and LP variants with disease specific subgroups (E) or 2017 ELN risk categories (F) based on available information for 52 and 40 patients, respectively, compared with the whole cohort recruitment for those categories. P and LP variants identified in tier 1 genes only are shown on the right side. (G-H) Percentage frequency of P and LP variants classified by gender and age where denominator is the number of samples in that particular group within 391 patients. A subset of patients with germline P and LP variants identified in the tier 1 genes is presented in the graphs on the right. (I) Genes harboring number of P and LP variants in each of 3 age groups. ** indicates P value <.01. AEL, acute erythroid leukemia; AML NOS, acute myeloid leukemia, NOS; AML NPM1mut, AML with mutated NPM1; AML with CBFB-MYH11, AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11; AML with KMT2A-MLLT3, AML with t(9;11)(p22;q23); KMT2A-MLLT3; AML with RPN1-EVI1, AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1; AML-MRC, AML with myelodysplasia-related changes; AMML, acute myelomonocytic leukemia; AMoL, acute monoblastic and monocytic leukemia; tMNs, therapy-related myeloid neoplasms.

Close Modal
This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal