A clinical perspective on immunoglobulin heavy chain clonal heterogeneity in B cell acute lymphoblastic leukemia

Fries, Carol; Burack, W. Richard

doi:10.1016/j.leukres.2018.10.018

Cited by 5 publications

(6 citation statements)

References 64 publications

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“…The heterogeneity and clonal evolution of B-ALL have been extensively studied. 21 The significance of the heterogeneity of IGH/IGL sequences in B-ALL lineage switch is not known.…”

Section: Discussionmentioning

confidence: 99%

Lineage Switch in an Infant B-Lymphoblastic Leukemia With t(1;11)(p32;q23); KMT2A/EPS15, Following Blinatumomab Therapy

Chisholm

Tsuchiya

et al. 2021

Pediatr Dev Pathol

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We report a 6 month-old infant girl with t(1;11)(p32;q23), KMT2A/EPS15-rearranged B-acute lymphoblastic leukemia (B-ALL) that was refractory to traditional ALL-directed chemotherapy. Following administration of blinatumomab, she experienced lineage switch from B-ALL to acute myeloid leukemia (AML). Myeloid-directed chemotherapy resulted in clearance of AML by flow cytometry, though a residual CD19+ B-ALL population persisted (0.14%). Following bridging blinatumomab, the patient achieved B-ALL and AML remission, as measured by flow cytometry. The patient subsequently underwent allogeneic hematopoietic stem cell transplant. Unfortunately, she relapsed with CD19+ B-ALL one-month post-transplantation. Next generation sequencing study of IGH/IGL using ClonoSEQ® analysis detected 3 dominant sequences all present in her original B-ALL, lineage switched AML, and post-transplant relapsed B-ALL, though the latter showed an additional 4 sequences, three of which were present at low abundance in the original diagnostic sample. The presence of the same clones throughout her disease course suggests cellular reprogramming and differentiation following chemotherapy and immunotherapy. This is the first reported case of lineage switch of B-ALL with t(1;11) and also the first report of a lineage switch case that used ClonoSEQ® to define the clonality of the original B-ALL, lineage switched AML, and relapsed B-ALL.

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“…The heterogeneity and clonal evolution of B-ALL have been extensively studied. 21 The significance of the heterogeneity of IGH/IGL sequences in B-ALL lineage switch is not known.…”

Section: Discussionmentioning

confidence: 99%

Lineage Switch in an Infant B-Lymphoblastic Leukemia With t(1;11)(p32;q23); KMT2A/EPS15, Following Blinatumomab Therapy

Chisholm

Tsuchiya

et al. 2021

Pediatr Dev Pathol

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“…A total of 27 D gene segments and 9 JH segments comprise 23 and 6 functional components, respectively [ 37 ]. The possible VH/D/JH combinations and SHM that occur in hotspots endow the complementarity determining regions 3 (CDR3) of BCRs with the ability to interact with distinct antigen epitopes and serve as a fingerprint when recognizing and tracking the specific B-cell [ 12 ]. Similar processes occur at the IGK or IGL locus, within which 34–38 and 29–33 functional segments can be selected from a total of 76 Vκ and 73–74 Vλ genes, respectively [ 38 ].…”

Section: Targets Utilized For Mrd Monitoring By Ngsmentioning

confidence: 99%

“…MRD is generally acknowledged as one of the most powerful approaches for the prediction of relapse and prognosis. MRD-positive patients have far less favorable event-free survival outcomes than MRD-negative patients [ 10 – 12 , 15 , 22 , 88 – 91 ]. The prognostic value of MRD among patients undergoing specific treatments is mainly reflected in the dynamic risk-stratification ability.…”

Section: Mrd Monitoring Through Clonality Assessment By Ngsmentioning

confidence: 99%

Next-generation sequencing for MRD monitoring in B-lineage malignancies: from bench to bedside

et al. 2022

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Minimal residual disease (MRD) is considered the strongest relevant predictor of prognosis and an effective decision-making factor during the treatment of hematological malignancies. Remarkable breakthroughs brought about by new strategies, such as epigenetic therapy and chimeric antigen receptor-T (CAR-T) therapy, have led to considerably deeper responses in patients than ever, which presents difficulties with the widely applied gold-standard techniques of MRD monitoring. Urgent demands for novel approaches that are ultrasensitive and provide sufficient information have put a spotlight on high-throughput technologies. Recently, advances in methodology, represented by next-generation sequencing (NGS)-based clonality assays, have proven robust and suggestive in numerous high-quality studies and have been recommended by some international expert groups as disease-monitoring modalities. This review demonstrates the applicability of NGS-based clonality assessment for MRD monitoring of B-cell malignancies by summarizing the oncogenesis of neoplasms and the corresponding status of immunoglobulin (IG) rearrangements. Furthermore, we focused on the performance of NGS-based assays compared with conventional approaches and the interpretation of results, revealing directions for improvement and prospects in clinical practice.

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“…389 ► A clinical perspective on immunoglobulin heavy chain clonal heterogeneity in B cell acute lymphoblastic leukemia. 390 Flow cytometry classically provided lower sensitivity than molecular techniques. However, next-generation flow cytometry (NGF) approaches reach sensitivities comparable with molecular methods, and have the advantage of faster turnaround times, broader applicability, and lower cost.…”

Section: Discussionmentioning

confidence: 99%

SITC cancer immunotherapy resource document: a compass in the land of biomarker discovery

Hu‐Lieskovan

Bhaumik

Dhodapkar

et al. 2020

J Immunother Cancer

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Since the publication of the Society for Immunotherapy of Cancer’s (SITC) original cancer immunotherapy biomarkers resource document, there have been remarkable breakthroughs in cancer immunotherapy, in particular the development and approval of immune checkpoint inhibitors, engineered cellular therapies, and tumor vaccines to unleash antitumor immune activity. The most notable feature of these breakthroughs is the achievement of durable clinical responses in some patients, enabling long-term survival. These durable responses have been noted in tumor types that were not previously considered immunotherapy-sensitive, suggesting that all patients with cancer may have the potential to benefit from immunotherapy. However, a persistent challenge in the field is the fact that only a minority of patients respond to immunotherapy, especially those therapies that rely on endogenous immune activation such as checkpoint inhibitors and vaccination due to the complex and heterogeneous immune escape mechanisms which can develop in each patient. Therefore, the development of robust biomarkers for each immunotherapy strategy, enabling rational patient selection and the design of precise combination therapies, is key for the continued success and improvement of immunotherapy. In this document, we summarize and update established biomarkers, guidelines, and regulatory considerations for clinical immune biomarker development, discuss well-known and novel technologies for biomarker discovery and validation, and provide tools and resources that can be used by the biomarker research community to facilitate the continued development of immuno-oncology and aid in the goal of durable responses in all patients.

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A clinical perspective on immunoglobulin heavy chain clonal heterogeneity in B cell acute lymphoblastic leukemia

Cited by 5 publications

References 64 publications

Lineage Switch in an Infant B-Lymphoblastic Leukemia With t(1;11)(p32;q23); KMT2A/EPS15, Following Blinatumomab Therapy

Lineage Switch in an Infant B-Lymphoblastic Leukemia With t(1;11)(p32;q23); KMT2A/EPS15, Following Blinatumomab Therapy

Next-generation sequencing for MRD monitoring in B-lineage malignancies: from bench to bedside

SITC cancer immunotherapy resource document: a compass in the land of biomarker discovery

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