The NeoTYPE ALL Profile analyzes 39 genes to detect DNA and RNA alterations through a combination of next-generation sequencing (NGS) and FISH as noted below. Test reports include a summary interpretation of all results together. FISH components may be ordered as “Tech-Only” by pathology clients who wish to perform the professional component. Test may be ordered as “Molecular only” by clients who wish to opt out of the FISH components.
- DNA Sequencing:
- SNVs/InDels (21 Genes): ABL1, ABL2, CDKN2A, CRLF2, CSF1R, EPOR, FGFR2, FGFR3, FLT3, IKZF1, IL7R, JAK1, JAK2, JAK3, NTRK1, NTRK2, NTRK3, PDGFRA, PDGFRB, SH2B3, and TP53
- Copy Number Variations (3 Genes): CDKN2A, IKZF1, and TP53
Note: Only copy number loss is reported as it is a clinically relevant abnormality for these tumor suppressor genes.
- RNA Sequencing:
- Fusions (30 Genes): ABL1, ABL2, BCR, CRLF2, CSF1R, EPOR, ETV6, FGFR1, FLT3, IKZF1, JAK2, KMT2A, MEF2D, MLLT10, NTRK1, NTRK2, NTRK3, NUP98, PAX5, PBX1, PDGFRA, PDGFRB, PTK2B, RUNX1, TAL1, TCF3, TLX1, TLX3, TYK2, and ZNF384
- Gene Overexpression (2 Genes): CRLF2 and EPOR
- FISH (2 Genes): CRLF2 (Xp22.33/Yp11.32) | EPOR (19p13.2)
The NeoTYPE ALL Profile is intended as an aid in diagnostic subtyping, risk assessment, and therapy selection of acute lymphoblastic leukemia (ALL) with a focus on Ph+ and Ph-like B-ALL subtypes. It is appropriate for both adult and pediatric ALL patients.
Comprehensive genetic information is of critical importance for disease management of ALL.
- 25% of B-ALL cases have the BCR-ABL1 fusion (Philadelphia chromosome-positive, or Ph+), with historically poor outcomes, but improved with tyrosine kinase inhibitors1.
- Approximately 20-25% of B-ALL cases are characterized as Ph-Like and associated with a highly unfavorable prognosis2,3.
- Many fusions, such as those involving ABL1, ABL2, CSF1R, PDGFRB, JAK2, or EPOR, may be responsive to certain tyrosine kinase inhibitors2.
- Oncogenic RNA overexpression, often resulting from gene fusions, may provide prognostic information for ALL. High expression of CRLF2 or EPOR correlates with an unfavorable prognosis and poor response to conventional therapy4,5.
- Copy number variations are increasingly relevant as risk stratification markers for ALL. Deletions of tumor suppressor genes, such as CDKN2A, IKZF1 and TP53, are generally associated with poor clinical outcomes6,7,8.
- Bone Marrow Aspirate: 2-3 mL in EDTA tube
- Peripheral Blood: 3-5 mL in EDTA tube
- FFPE tissue: Paraffin block. Alternatively, send 1 H&E slide plus 10-14 unstained slides cut at 5 or more microns. Please use positively-charged slides and 10% NBF fixative is the recommended fixative. Do not use zinc or mercury fixatives (B5). Highly acidic or prolonged decalcification processes will not yield sufficient nucleic acid to accurately perform molecular studies. Note: not validated for the FISH portion.
Use refrigerated cold pack for transport. Make sure cold pack is not in direct contact with specimen. Ship same day as drawn whenever possible; specimens <72 hours old preferred.
Tech-only option available for FISH component
- Sánchez, R., Ribera, J., Morgades, M. et al. A novel targeted RNA-Seq panel identifies a subset of adult patients with acute lymphoblastic leukemia with BCR-ABL1-like characteristics. Blood Cancer J. 10, 43 (2020).
- Jain N, et al. Ph-like acute lymphoblastic leukemia: a high-risk subtype in adults. Blood. 2017;129(5):572-581.
- Terwilliger T , Abdul-Hay M. Acute lymphoblastic leukemia: a comprehensive review and 2017 update. Blood Cancer Journal (2017) 7, e577;
- Iacobucci I, Li Y, Roberts KG, et al. Truncating Erythropoietin Receptor Rearrangements in Acute Lymphoblastic Leukemia. Cancer Cell. 2016;29(2):186-200.
- Dou H, Chen X, Huang Y, et al. Prognostic significance of P2RY8-CRLF2 and CRLF2 overexpression may vary across risk subgroups of childhood B-cell acute lymphoblastic leukemia. Genes Chromosomes Cancer. 2017;56(2):135-146.
- Zhang W, Kuang P, Liu T. Prognostic significance of CDKN2A/B deletions in acute lymphoblastic leukaemia: a meta-analysis. Ann Med. 2019;51(1):28-40.
- Marke, R, van Leeuwen F, Scheijen B. The many faces of IKZF1 in B-cell precursor acute lymphoblastic leukemia. Haematologica. Vol.103 No. 4 (2018): April, 2018
- Stengel A. et al. TP53 mutations occur in 15.7% of ALL and are associated with MYC-rearrangement, low hypodiploidy, and a poor prognosis. Blood (2014) 124 (2):251-258.