Acute lymphoblastic leukemia (ALL) represents 3% of hematologic neoplasias and is a heterogeneous disease characterized by the proliferation of immature lymphoid cells in bone marrow, peripheral blood, and other organs.
Identification of specific recurrent genetic abnormalities is critical for disease evaluation, optimal risk stratification, and treatment planning. In addition different molecular aberrations (ph+ and ph like+ ALL, IKZF1 deletion, etc) are being utilized for prognostic counselling and selection of therapy approaches.
Assessed minimal residual disease (MRD) after treatment by NGS-assays to detect IGH rearrangements in ALL has been recommended in the follow-up of ALL patients (NCCN). MRD quantification with this method predicts long-term outcomes and identifies subsidiary patients who are to undergo allogeneic transplantation, assesses treatment response (TKIs, Immunotherapy or stem cell transplant), monitors remission status and detects early relapse.
The Altum test comprises a DNA-based multigene panel by NGS of bone marrow aspirates at diagnosis, and MRD testing in follow-up samples with NGS based assays to detect IGH rearrangements with a sensitivity of 1 in 106 nucleated cells in parallel with a NGS based assay to detect mutated genes identified in the diagnosis panel (Thermofisher platform), and provides a detailed clinical analysis of the results.
- Baseline VDJ clonotype detection by NGS.
- Mutational screening using a targeted NGS panel (35 genes).
- Mutational screening by whole exome NGS.
- Transcriptome profiling using RNA-seq.
- Gene expression analysis by RT-PCR.
- Targeted RNA-Seq panel to identify Ph-like phenotype.
- Rearrangement quantifications by RT-PCR : BCR-ABL1 (t9;22)*, TEL-AML1 (t12;21) and E2A-PBX1 (t1;19).
- CRLF2 expression by RT-PCR.
- MLPA for IKZF1 and CDKN2A/B deletions.
* Transcripts e13a2, e14a2, e1a2
Minimal residual disease (MRD) test
BCR-ABL rearrangement quantification by RT-PCR (p210 and p190).
- MRDeep: MRD assesment by VDJ clonotypes detection using NGS.
- CloneSight-ALL: MRD assesment in liquid biopsy by personalized tumor biomarkers monitoring using NGS.
- ClonEv-ALL: ultra-sensitive ABL1 kinase domain mutation detection using genomic DNA.