Disease characteristics
| . | Initial B-ALL diagnosis . | LS to AML . | Relapsed B-ALL . | |||
|---|---|---|---|---|---|---|
| Case 1 | ||||||
| Blast % | 93 B-lymphoblasts | 96 abnormal immature monocytes 0.14 B-lymphoblasts (immunophenotype similar to diagnosis) | 70 B-lymphoblasts | |||
| Flow cytometry immunophenotype of major blast population | CD19 | Positive | CD19 | Negative | CD19 | Positive |
| CD22 | Positive | CD22 | Negative | CD22 | Positive | |
| CD10 | Negative | CD10 | Negative | CD10 | Negative | |
| CD15 | Partial positive | CD15 | Positive | CD15 | Negative | |
| CD34 | Negative | CD34 | Negative | CD34 | Partial positive | |
| CD38 | Positive | CD38 | Positive | CD38 | Positive | |
| CD58 | Positive (increased) | CD58 | Positive | CD58 | Positive (increased) | |
| HLA-DR | Positive | HLA-DR | Positive | HLA-DR | Positive | |
| CD13 | Negative | CD13 | Negative | CD13/33 | Negative | |
| CD33 | Negative | CD33 | Positive | CD33 | Negative | |
| CD11b | Not evaluated | CD11b | Positive | CD11b | Not evaluated | |
| CD14 | Negative | CD14 | Partial positive | CD14 | Not evaluated | |
| CD64 | Not evaluated | CD64 | Positive | CD64 | Negative | |
| CD4 | Not evaluated | CD4 | Positive (dim) | CD4 | Not evaluated | |
| CD7 | Partial positive | CD7 | Negative | CD7 | Not evaluated | |
| CD45 | Positive (slightly dim) | CD45 | Positive | CD45 | Positive | |
| CD123 | Not evaluated | CD123 | Not evaluated | CD123 | Positive | |
| Cytogenetics | Karyotype: 46, XX, t(1;11)(p32;q23)[16]/46,XX[2] | Karyotype: 46, XX, t(1;11)(p32;q23)[5]/47,XX,t(1;11),+8[14]/46,XX[1] | Not performed | |||
| FISH: positive for a KMT2A rearrangement in 81% of nuclei (with loss of 3′ KMT2A signal) | FISH: positive for a KMT2A rearrangement in 95% of nuclei (loss of 3′ KMT2A signal) | |||||
| ClonoSEQ, % | IGH-SeqA = 60.9 IGH-SeqB = 70.0 IGL-SeqC = 76.2 IGL-SeqD = 60.9 IGH-SeqE = 0.6 IGH-SeqF = 1.8 IGH-SeqG = 0.0013 IGH-SeqH = ND | IGH-SeqA ≥ 99.9 IGH-SeqB ≥ 99.9 IGL-SeqC = 82.2 IGL-SeqD = ND IGH-SeqE = ND IGH-SeqF = ND IGH-SeqG = ND IGH-SeqH = ND | IGH-SeqA = 43.1 IGH-SeqB = 36.2 IGL-SeqC = 85.6 IGL-SeqD = ND IGH-SeqE = 68.4 IGH-SeqF = 67.4 IGH-SeqG = 68.5 IGH-SeqH = 68.5 | |||
| NGS | RNA fusion panel: positive for KMT2A-EPS15 fusion | DNA NGS panel: 1. Positive for the 3′ KMT2A deletion seen previously | Targeted testing (by DNA NGS): negative for NRAS p.G12C | |||
| DNA NGS panel: positive for 3′ KMT2A deletion | 2. New findings of trisomy 8, NRAS p.G12C, and low-level subclonal KRAS p.G13D. | |||||
| Case 2 | ||||||
| Blast % | 95.5 B-lymphoblasts | 4.5 abnormal immature monocytes | 25 B-lymphoblasts | |||
| Flow cytometry immunophenotype of major blast population | CD19 | Positive (increased) | CD19 | Negative | CD19 | Positive (increased) |
| CD22 | Positive | CD22 | Not evaluated | CD22 | Positive | |
| CD10 | Negative | CD10 | Not evaluated | CD10 | Negative | |
| CD15 | Not evaluated | CD15 | Positive | CD15 | Partial positive | |
| CD34 | Positive | CD34 | Negative | CD34 | Positive | |
| CD38 | Positive | CD38 | Positive | CD38 | Positive | |
| CD58 | Positive (increased) | CD58 | Not evaluated | CD58 | Positive (increased) | |
| HLA-DR | Positive | HLA-DR | Positive | HLA-DR | Positive | |
| CD13 | Negative | CD13 | Negative | CD13 | Negative | |
| CD33 | Negative | CD33 | Positive | CD33 | Negative | |
| CD11b | Not evaluated | CD11b | Not evaluated | CD11b | Not evaluated | |
| CD14 | Not evaluated | CD14 | Negative | CD14 | Not evaluated | |
| CD64 | Negative | CD64 | Positive | CD64 | Not evaluated | |
| CD7 | Negative | CD7 | Negative | CD7 | Not evaluated | |
| CD56 | Not evaluated | CD56 | Positive | CD56 | Negative | |
| CD45 | Positive (dim) | CD45 | Positive | CD45 | Positive | |
| CD123 | Negative | CD123 | Negative | CD123 | Not evaluated | |
| Cytogenetics | 46, XX, t(4;11)(q21;q23)[20]; | Karyotype not performed | 46, X, t(X;10)(q13;p13),t(4;11)(q21;q23),t(4;15)(p16;q22),t(8;14)(q22;q32)[15]//46,XY[5] | |||
| FISH: positive for KMT2A rearrangement in 100% of nuclei | FISH: positive for KMT2A rearrangement in 10.5% of nuclei | FISH: positive for KMT2A rearrangement in 30% of nuclei | ||||
| ClonoSEQ, % | (performed 2.5 months after diagnosis) IGH-SeqA = 4.0 IGH-SeqB = 3.8 IGH-SeqC = 0.036 | IGH-SeqA = 3.6 IGH-SeqB = 0.019 IGH-SeqC = 3.1 | IGH-SeqA = 20.9 IGH-SeqB = ND IGH-SeqC = ND | |||
| NGS | Not performed | Not performed | Not performed | |||
| . | Initial B-ALL diagnosis . | LS to AML . | Relapsed B-ALL . | |||
|---|---|---|---|---|---|---|
| Case 1 | ||||||
| Blast % | 93 B-lymphoblasts | 96 abnormal immature monocytes 0.14 B-lymphoblasts (immunophenotype similar to diagnosis) | 70 B-lymphoblasts | |||
| Flow cytometry immunophenotype of major blast population | CD19 | Positive | CD19 | Negative | CD19 | Positive |
| CD22 | Positive | CD22 | Negative | CD22 | Positive | |
| CD10 | Negative | CD10 | Negative | CD10 | Negative | |
| CD15 | Partial positive | CD15 | Positive | CD15 | Negative | |
| CD34 | Negative | CD34 | Negative | CD34 | Partial positive | |
| CD38 | Positive | CD38 | Positive | CD38 | Positive | |
| CD58 | Positive (increased) | CD58 | Positive | CD58 | Positive (increased) | |
| HLA-DR | Positive | HLA-DR | Positive | HLA-DR | Positive | |
| CD13 | Negative | CD13 | Negative | CD13/33 | Negative | |
| CD33 | Negative | CD33 | Positive | CD33 | Negative | |
| CD11b | Not evaluated | CD11b | Positive | CD11b | Not evaluated | |
| CD14 | Negative | CD14 | Partial positive | CD14 | Not evaluated | |
| CD64 | Not evaluated | CD64 | Positive | CD64 | Negative | |
| CD4 | Not evaluated | CD4 | Positive (dim) | CD4 | Not evaluated | |
| CD7 | Partial positive | CD7 | Negative | CD7 | Not evaluated | |
| CD45 | Positive (slightly dim) | CD45 | Positive | CD45 | Positive | |
| CD123 | Not evaluated | CD123 | Not evaluated | CD123 | Positive | |
| Cytogenetics | Karyotype: 46, XX, t(1;11)(p32;q23)[16]/46,XX[2] | Karyotype: 46, XX, t(1;11)(p32;q23)[5]/47,XX,t(1;11),+8[14]/46,XX[1] | Not performed | |||
| FISH: positive for a KMT2A rearrangement in 81% of nuclei (with loss of 3′ KMT2A signal) | FISH: positive for a KMT2A rearrangement in 95% of nuclei (loss of 3′ KMT2A signal) | |||||
| ClonoSEQ, % | IGH-SeqA = 60.9 IGH-SeqB = 70.0 IGL-SeqC = 76.2 IGL-SeqD = 60.9 IGH-SeqE = 0.6 IGH-SeqF = 1.8 IGH-SeqG = 0.0013 IGH-SeqH = ND | IGH-SeqA ≥ 99.9 IGH-SeqB ≥ 99.9 IGL-SeqC = 82.2 IGL-SeqD = ND IGH-SeqE = ND IGH-SeqF = ND IGH-SeqG = ND IGH-SeqH = ND | IGH-SeqA = 43.1 IGH-SeqB = 36.2 IGL-SeqC = 85.6 IGL-SeqD = ND IGH-SeqE = 68.4 IGH-SeqF = 67.4 IGH-SeqG = 68.5 IGH-SeqH = 68.5 | |||
| NGS | RNA fusion panel: positive for KMT2A-EPS15 fusion | DNA NGS panel: 1. Positive for the 3′ KMT2A deletion seen previously | Targeted testing (by DNA NGS): negative for NRAS p.G12C | |||
| DNA NGS panel: positive for 3′ KMT2A deletion | 2. New findings of trisomy 8, NRAS p.G12C, and low-level subclonal KRAS p.G13D. | |||||
| Case 2 | ||||||
| Blast % | 95.5 B-lymphoblasts | 4.5 abnormal immature monocytes | 25 B-lymphoblasts | |||
| Flow cytometry immunophenotype of major blast population | CD19 | Positive (increased) | CD19 | Negative | CD19 | Positive (increased) |
| CD22 | Positive | CD22 | Not evaluated | CD22 | Positive | |
| CD10 | Negative | CD10 | Not evaluated | CD10 | Negative | |
| CD15 | Not evaluated | CD15 | Positive | CD15 | Partial positive | |
| CD34 | Positive | CD34 | Negative | CD34 | Positive | |
| CD38 | Positive | CD38 | Positive | CD38 | Positive | |
| CD58 | Positive (increased) | CD58 | Not evaluated | CD58 | Positive (increased) | |
| HLA-DR | Positive | HLA-DR | Positive | HLA-DR | Positive | |
| CD13 | Negative | CD13 | Negative | CD13 | Negative | |
| CD33 | Negative | CD33 | Positive | CD33 | Negative | |
| CD11b | Not evaluated | CD11b | Not evaluated | CD11b | Not evaluated | |
| CD14 | Not evaluated | CD14 | Negative | CD14 | Not evaluated | |
| CD64 | Negative | CD64 | Positive | CD64 | Not evaluated | |
| CD7 | Negative | CD7 | Negative | CD7 | Not evaluated | |
| CD56 | Not evaluated | CD56 | Positive | CD56 | Negative | |
| CD45 | Positive (dim) | CD45 | Positive | CD45 | Positive | |
| CD123 | Negative | CD123 | Negative | CD123 | Not evaluated | |
| Cytogenetics | 46, XX, t(4;11)(q21;q23)[20]; | Karyotype not performed | 46, X, t(X;10)(q13;p13),t(4;11)(q21;q23),t(4;15)(p16;q22),t(8;14)(q22;q32)[15]//46,XY[5] | |||
| FISH: positive for KMT2A rearrangement in 100% of nuclei | FISH: positive for KMT2A rearrangement in 10.5% of nuclei | FISH: positive for KMT2A rearrangement in 30% of nuclei | ||||
| ClonoSEQ, % | (performed 2.5 months after diagnosis) IGH-SeqA = 4.0 IGH-SeqB = 3.8 IGH-SeqC = 0.036 | IGH-SeqA = 3.6 IGH-SeqB = 0.019 IGH-SeqC = 3.1 | IGH-SeqA = 20.9 IGH-SeqB = ND IGH-SeqC = ND | |||
| NGS | Not performed | Not performed | Not performed | |||
AML, acute myeloid leukemia; FISH, fluorescence in situ hybridization; LS, lineage switch; ND, not detected; NGS, next-generation sequencing.