{ "metadata": { "name": "MRS. PUSHPA GUPTA", "cr_no": "EXT129726(394394)", "age_sex": "48Y/Female", "referred_doctor": "Dr. NARENDER AGARWAL", "sample_type": "Bone Marrow Aspirate", "diagnosis": "B-cell Lineage Acute Lymphoblastic Leukemia", "tumor_fraction": "", "order_no": "", "order_date": "04.08.2026", "receiving_date": "04.08.2026", "reporting_date": "26.08.2026", "lab_id": "2026216-1793" }, "report_information": { "panel_title": "Archer FusionPlex Acute lymphoblastic leukemia (ALL) Panel" }, "clinical_content": { "sections": [ { "heading": "_preamble", "order": 1, "content": "BLAST: 69% (BMA1420/826 Myelogram)", "page": 1, "source_lines": [ 61 ] }, { "heading": "Report Highlights", "order": 2, "content": "Alteration detected", "page": 1, "source_lines": [ 63 ], "children": [ { "kind": "list_item", "content": "BCR::ABL1 fusion (p190; e1a2)", "page": 1, "order": 3 }, { "kind": "list_item", "content": "IKZF1 Δ4–7 intragenic deletion", "page": 1, "order": 4 }, { "heading": "RNA Sequence Variants", "order": 5, "page": 1, "source_lines": [ 87 ], "children": [ { "kind": "table", "headers": [ "Fusion Detected", "Breakpoint", "Reading Frame", "Supporting Reads", "Unique Start Sites", "Reads per" ], "rows": [ [ "BCR(1)::ABL1(2)", "chr22:23524426-chr9:133729451", "In-Frame", "215", "1301", "(%) million/Reads 57.21" ], [ "IKZF1(3)-IKZF1(8)", "chr7:50367353-chr7:50467616", "In-Frame", "390", "5950", "40.69" ] ], "order": 6 }, { "heading": "Genomic Assembly", "order": 7, "content": "GrCH 37(hg19)", "page": 1, "source_lines": [ 67 ] } ] }, { "heading": "Interpretation Summary", "order": 8, "content": "BCR::ABL1 p190 (e1a2) is a defining oncogenic driver of Ph-positive B-ALL and provides a target for ABL1 tyrosine kinase inhibitor\ntherapy (PMID:3460176, 2825022, 11345193, 35277197).IKZF1 Δ4–7 is a pathogenic, dominant-negative alteration associated\nwith adverse outcomes in B-ALL; however, its independent prognostic significance in BCR::ABL1-positive disease remains uncertain\n(PMID:19770381, 27067989).", "page": 1, "source_lines": [ 68, 69, 70, 71, 72 ] }, { "heading": "Clinical Significance", "order": 9, "page": 1, "source_lines": [ 111 ], "children": [ { "heading": "Variant:BCR(1)::ABL1(2) Fusion (p190;e1a2)", "order": 10, "page": 1, "source_lines": [ 74 ], "children": [ { "heading": "Pathogenic Contribution", "order": 11, "content": "BCR::ABL1 fusion is a well-established oncogenic driver, resulting in constitutive tyrosine kinase activity and activation of\ndownstream JAK/STAT and PI3K signaling, promoting proliferation, survival, and cellular transformation. It is characteristic\nof a subset of ALL (PMID:3460176, 2825022, 11345193).The p190 (e1a2) transcript is the predominant BCR::ABL1 isoform\nin Ph-positive B-ALL and is detected in approximately 65% of adult Ph-positive ALL cases (PMID:35277197).", "page": 1, "source_lines": [ 75, 76, 77, 78, 79 ] }, { "heading": "Predictive/Therapeutic Significance", "order": 12, "content": "The multikinase inhibitors imatinib, dasatinib and ponatinib are FDA-approved for the treatment of patients with BCR-", "page": 1, "source_lines": [ 81, 82 ] }, { "heading": "Prognostic Significance", "order": 13, "content": "The p190 (e1a2)BCR::ABL1 transcript is the predominant isoform in Ph-positive B-ALL, accounting for 199/305 (65%) cases\nversus 106/305 (35%) with p210 in a cohort of consecutive adults (PMID:35277197). Although Ph-positive B-ALL is\nhistorically considered a high-risk entity, the prognostic significance of p190 versus p210 remains uncertain in the TKI era.\nA meta-analysis of 9 studies comprising 1,582 patients found a modest association of p210 with inferior EFS (HR 1.34, 95%\nCI 1.05–1.72), but no significant difference in OS (HR 1.15, 95% CI 0.92–1.45); the authors suggested that this distinction\nmay be attenuated by the use of second- and third-generation TKIs (PMID:33338050). Consistent with this, contemporary\ndata generally show comparable outcomes between p190 and p210, although some cohorts have reported relatively more\nfavorable outcomes with p190; notably, p210 was independently associated with inferior OS in the 305-patient cohort\n(HR 1.692, 95% CI 1.009–2.838; p=0.046) (PMID:35277197).", "page": 1, "source_lines": [ 84, 85, 86, 170, 171, 172, 173, 174, 175, 176 ] } ] }, { "heading": "Variant:IKZF1 Δ4–7 intragenic deletion", "order": 15, "page": 2, "source_lines": [ 182 ], "children": [ { "heading": "Pathogenic Contribution", "order": 16, "content": "IKZF1 Δ4–7 is a pathogenic intragenic deletion that produces the IK6 isoform, which lacks exons 4–7 encoding the N-\nterminal DNA-binding zinc fingers while retaining the C-terminal dimerization domain. This results in a dominant-negative\nloss of IKZF1 transcriptional function, impairing normal B-cell differentiation and promoting leukemic proliferation.IKZF1\nloss also cooperates with BCR::ABL1-mediated tyrosine-kinase signaling in B-ALL pathogenesis (PMID:29519871).", "page": 2, "source_lines": [ 183, 184, 185, 186, 187 ] }, { "heading": "Predictive/Therapeutic Significance", "order": 17, "content": "There are no FDA-approved or NCCN-compendium listed treatments specifically for patients with IKZF1 deletion B-", "page": 2, "source_lines": [ 189, 190 ] }, { "heading": "Prognostic Significance", "order": 18, "content": "IKZF1 Δ4–7 has been associated with adverse outcome in adult BCR::ABL1-positive ALL, including shorter disease-free\nsurvival and increased relapse risk (PMID:19770381). However, the prognostic impact of IKZF1 deletion in the TKI era is\nnot entirely consistent. In an adult B-ALL cohort, the adverse effect of IKZF1 deletion was mainly observed in BCR::ABL1-\nnegative disease, with no significant outcome difference among BCR::ABL1-positive patients (PMID:27067989).\nTherefore, in p190 BCR::ABL1-positive B-ALL,IKZF1 Δ4–7 should be considered a potentially adverse/cooperating\nalteration, but its independent prognostic significance is uncertain and should not be used alone for risk stratification.", "page": 2, "source_lines": [ 193, 194, 195, 196, 197, 198, 199 ] } ] } ] }, { "heading": "Assay Information and Methodology", "order": 20, "content": "RIN/DV200%:7.2/98.17%\no\nTotal unique fragments:582,799\no\nOn Target %:99.3%\no\nRNA QC Status: PASS\nTotal RNA unique fragments: 370,942\nAverage Unique RNA Start Sites per GSP2: 121.61\nAverage Unique RNA Start Sites per GSP2 Control: 187.38\no\nDNA QC Status: PASS\nTotal DNA unique fragments: 103,797\nAverage Unique DNA Start Sites per GSP2:65.27\nAverage Unique DNA Start Sites per GSP2 Control: 61.12\nAnalytical Sensitivity and Limitations:Assay performance may be affected by tumor cellularity, RNA quality, specimen preservation, and fusion\ntranscript expression levels. A negative result does not exclude the presence of alterations outside assay coverage or below the validated limit of\ndetection.", "page": 2, "source_lines": [ 205, 291, 292, 293, 294, 295, 297, 298, 300, 302, 304, 307, 308, 310, 312, 314, 317, 318, 319 ], "children": [ { "heading": "Test Description", "order": 21, "content": "– This customized panel is a targeted next-generation sequencing (NGS)-based RNA fusion assay utilizing the Archer FusionPlex ALL\nPanel for detection of clinically relevant gene fusions and rearrangements associated with lymphoid malignancies using 506 GSPs targeting 81 genes.\nThe assay employs Anchored Multiplex PCR (AMP™) technology for identification of both known and novel fusion partners from formalin-fixed paraffin-\nembedded (FFPE) tumor tissue TNA (Total Nucleic Acid)/RNA.\nGenes Analyzed for Rearrangements/SNVs– ABL1, ABL2, AICDA, BCL11B, BCL2, BCL6, BCR, BLNK, BRAF, CD274, CHD1, CREBBP, CRLF2, CSF1R, CTLA4,\nDNM2, DNTT, EBF1, EPOR, ETV6, EZH2, FBXW7, FGFR1, FLT3, HOXA10, HOXA9, IDH1, IDH2, IKZF1, IKZF2, IKZF3, IL7R, IRF4, IRF8, JAK1, JAK2, JAK3, KDM6A,\nKLF2, KMT2A, KRAS, LMO1, LYL1, MLLT4, MPL, MYC, NF1, NOTCH1, NRAS, NT5C2, NTRK3, NUP214, NUP98, P2RY8, PAG1, PAX5, PBX1, PDCD1, PDCD1LG2,\nPDGFRA, PDGFRB, PICALM, PTK2B, PTPN11, RAG1, RAG2, RUNX1, SEMA6A, SETD2, SH2B3, SOX11, STAT3, STAT5B, STIL, TAL1, TCF3, TLX1, TLX3, TYK2,\nWT1, ZCCHC7\nThe assay utilizes a minimum input of 20 ng total nucleic acid (TNA), and libraries are sequenced to a minimum depth of 1.5 million reads. Sequencing\ndata are processed and analyzed using Archer Analysis Pipeline version 7.5.1 for detection and reporting of gene fusions, rearrangements, and single\nnucleotide variants (SNVs).\nVariants of strong and potential clinical significance are only reported in somatic panels.", "page": 2, "source_lines": [ 208, 209, 210, 211, 214, 215, 275, 276, 277, 280, 281, 282, 285 ] }, { "heading": "Disclaimer", "order": 23, "content": "The information in this report does not constitute a treatment recommendation or recommendation to not use any specific therapeutic agent, and\nit should not be interpreted as treatment advice. Decisions concerning patient care and treatment rest solely within the discretion of the patient's treating\nphysician.", "page": 3, "source_lines": [ 321, 322, 323 ] } ] } ] } ] }, "authorization": { "performed_by": "Mamta Arya Scientist C\nAmit Negi Scientist A\nMolecular Diagnostics", "reviewed_by": "Dr Rushali Saxena\nAttending consultant, Pathology", "approved_by": "Dr. Anurag Mehta\nPrincipal Director Laboratory Services\nRajiv Gandhi Cancer Institute & Research Centre.\nRohini, New Delhi." }, "processing": { "source_file": "/app/uploads/29384_TranSeq ALL NGS.pdf", "content_hash": "5e564069005325d80976c29489f9f7071b98bf3cd9f87c04bd0704d1f31716ca", "processed_at": "2026-09-12T10:35:13.255510+00:00", "pipeline_version": "1.0.0", "pipeline_name": "molecular", "pages": 3, "sections_detected": 2, "warnings_count": 1, "skipped_image_blocks": 3, "skipped_figure_lines": 0, "content_coverage": 0.9971, "validation_status": "PASSED", "validation_failures": [], "validation_warnings": [], "header_layout": "B" } }