Role of CD81 and CD58 in minimal residual disease detection in pediatric B lymphoblastic leukemia

Tsitsikov, Erdyni; Harris, Marian H.; Silverman, Lewis B.; Sallan, Stephen E.; Weinberg, Olga K.

doi:10.1111/ijlh.12795

Cited by 18 publications

(20 citation statements)

References 22 publications

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“…MRD is detected at levels greater than or equal to one leukemia cell in 10 3 normal cells at the end of induction therapy as previously described . In cases where molecular MRD was not performed, MRD was assessed by percentage of blasts on flow cytometry as previously described …”

Section: Methodsmentioning

confidence: 99%

Genomic and clinical characterization of B/T mixed phenotype acute leukemia reveals recurrent features and T‐ALL like mutations

Griffin

Lee

et al. 2018

American J Hematol

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The B/T subtype of mixed phenotype acute leukemia (B/T MPAL) is defined by co-expression of antigens of both B- and T-cell lineages on leukemic blasts. Although it has been suggested that multilineage antigen expression portends poor response to chemotherapy, the clinical characteristics and driver mutations that underlie the pathogenesis of this rare subtype of acute leukemia are scarcely known. We identified nine cases of B/T MPAL from multiple institutions and correlated clinical and immunophenotypic findings with next-generation sequencing data. We report that B/T MPAL commonly presents with lymphadenopathy in adolescence and young adulthood. While the tumors have diverse cytogenetic and genomic perturbations, recurrent acquired aberrations include mutations in the putative transcriptional regulator PHF6 and the JAK-STAT and Ras signaling pathways. Alterations were also identified in genes encoding hematopoietic transcription factors, cell cycle regulators/tumor suppressors, and chromatin modifying enzymes. The genomic landscape of B/T MPAL strongly resembles that of T-ALL subgroups associated with early developmental arrest, while genetic alterations that are common in B-ALL were rarely seen. Two-thirds of the patients responded to ALL-based chemotherapy with or without stem cell transplantation. Our observations lay the groundwork for further study of the unique biology and clinical trajectory of B/T MPAL.

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Section: Methodsmentioning

confidence: 99%

Genomic and clinical characterization of B/T mixed phenotype acute leukemia reveals recurrent features and T‐ALL like mutations

Griffin

Lee

et al. 2018

American J Hematol

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“…Survival was significantly shorter (6.6m vs 13.5m). A recent study highlights the importance of using multiple markers to detect MRD in B lymphoblastic leukemia [20]. Two case control studies of B-ALL patients and control participations at diagnosis and after 2-3 weeks of induction chemotherapy suggested that CD34/CD123 [21] and CD10/CD19/CD34 with CD45 or CD97 [22] are more specific for MRD detection in B-ALL.…”

Section: Discussionmentioning

confidence: 99%

Isolation and characterization of a CD34+ sub-clone in B-cell lymphoma

et al. 2020

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Non-Hodgkin's lymphoma (NHL) is the most common hematological malignancy in the US. Many types remain incurable despite response to initial therapy and achievement of complete remission (CR). Advanced laboratory techniques like multicolor flow cytometry (FCM) and polymerase chain reaction (PCR) have demonstrated persistence of rare malignant cell population post therapy. However, the functional and biological characteristics of this population have not been elucidated. Established B-lymphoma cell lines (B-NHL) and patient-derived samples (PDS) were analyzed using 8-color FCM. CD34 + sub-population was enriched using in vitro exposure to 2-chlorodeoxyadenosine (2-CdA) and by CD34 magnetic beads. Genetic analysis of cell fractions was done by karyotyping and array comparative genomic hybridization (aCGH). Sensitivity to chemotherapy was assayed by short-term in vitro exposure to chemotherapy. Clonogenicity was determined by soft agar colony formation assay, and proliferation was determined using DNA staining with propidium iodide and FCM. FCM demonstrated the presence of a minute sub-clone of monotypic B-cells that express CD34 in B-NHL cell lines (3 of 3) and in PDS (8 of 8). This sub-population enriched up to 50 fold in vitro by exposure to 2-CdA and up to 80% purity by CD34 magnetic bead column isolation. Except for CD34 expression, this population expressed identical phenotype and genotype to parent cells, but was more proliferative, Hoechst 33342-positive, clonogenic, and resistant to chemotherapy compared with the CD34population. The isolated CD34 + monotypic B-cells may contribute to resistance of certain NHL to treatment and should be targeted by potential new drugs for NHL.

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“…In the same line of thought, the loss of CD19 antigen expression at the surface of leukemic cells enabling the tumor to evade chimeric antigen receptor (CAR) immunotherapy [ 48 , 49 ] is a well-known representative example of antigen plasticity and evolved adaptation of leukemic cells upon the treatment. Therefore, the identification of several stable surface markers aberrantly expressed in leukemic cells is critical to follow the disease evolution and to monitor resistant cells [ 50 , 51 ]. Together, phenotypic and functional plasticity should be considered in experimental approaches to identify LSC-enriched populations, but also at the clinical level to explain therapy escape mechanisms and B-ALL relapse.…”

Section: Cellular and Molecular Heterogeneity In Acute Leukemia: In Search Of Leukemic Stem Cellsmentioning

confidence: 99%

Oncogene-Induced Reprogramming in Acute Lymphoblastic Leukemia: Towards Targeted Therapy of Leukemia-Initiating Cells

Fregona

Bayet

Gerby

2021

Cancers

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Our understanding of the hierarchical structure of acute leukemia has yet to be fully translated into therapeutic approaches. Indeed, chemotherapy still has to take into account the possibility that leukemia-initiating cells may have a distinct chemosensitivity profile compared to the bulk of the tumor, and therefore are spared by the current treatment, causing the relapse of the disease. Therefore, the identification of the cell-of-origin of leukemia remains a longstanding question and an exciting challenge in cancer research of the last few decades. With a particular focus on acute lymphoblastic leukemia, we present in this review the previous and current concepts exploring the phenotypic, genetic and functional heterogeneity in patients. We also discuss the benefits of using engineered mouse models to explore the early steps of leukemia development and to identify the biological mechanisms driving the emergence of leukemia-initiating cells. Finally, we describe the major prospects for the discovery of new therapeutic strategies that specifically target their aberrant stem cell-like functions.

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Role of CD81 and CD58 in minimal residual disease detection in pediatric B lymphoblastic leukemia

Abstract: Our study highlights importance of using multiple markers to detect MRD in B lymphoblastic leukemia. Our findings indicate that including both CD58 and CD81 markers in addition to CD19, CD34, CD20, CD38, and CD10 are helpful in MRD detection by flow cytometry.

Cited by 18 publications

References 22 publications

Genomic and clinical characterization of B/T mixed phenotype acute leukemia reveals recurrent features and T‐ALL like mutations

Genomic and clinical characterization of B/T mixed phenotype acute leukemia reveals recurrent features and T‐ALL like mutations

Isolation and characterization of a CD34+ sub-clone in B-cell lymphoma

Oncogene-Induced Reprogramming in Acute Lymphoblastic Leukemia: Towards Targeted Therapy of Leukemia-Initiating Cells

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