A comparative study of bone marrow and peripheral blood CD34<sup>+</sup> myeloblasts in acute myeloid leukaemia

Cheung, Alice; Chow, Howard C.H.; Liang, Raymond; Leung, Anskar Y.H.

doi:10.1111/j.1365-2141.2008.07431.x

Cited by 11 publications

(3 citation statements)

References 46 publications

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“…This observation suggested that PB and BM samples perform similarly. However, previous reports have shown differences in signal between PB/BM [25–28]. It might be expected that early emergent disease would be easier to detect in BM vs. PB due to the cellular make-up of both specimen types and potential for delayed mobilization to the periphery.…”

Section: Resultsmentioning

confidence: 95%

Measurable residual disease monitoring for patients with acute myeloid leukemia following hematopoietic cell transplantation using error corrected hybrid capture next generation sequencing

et al. 2019

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Improved systems for detection of measurable residual disease (MRD) in acute myeloid leukemia (AML) are urgently needed, however attempts to utilize broad-scale next-generation sequencing (NGS) panels to perform multi-gene surveillance in AML post-induction have been stymied by persistent premalignant mutation-bearing clones. We hypothesized that this technology may be more suitable for evaluation of fully engrafted patients following hematopoietic cell transplantation (HCT). To address this question, we developed a hybrid-capture NGS panel utilizing unique molecular identifiers (UMIs) to detect variants at 0.1% VAF or below across 22 genes frequently mutated in myeloid disorders and applied it to a retrospective sample set of blood and bone marrow DNA samples previously evaluated as negative for disease via standard-of-care short tandem repeat (STR)-based engraftment testing and hematopathology analysis in our laboratory. Of 30 patients who demonstrated trackable mutations in the 22 genes at eventual relapse by standard NGS analysis, we were able to definitively detect relapse-associated mutations in 18/30 (60%) at previously disease-negative timepoints collected 20–100 days prior to relapse date. MRD was detected in both bone marrow (15/28, 53.6%) and peripheral blood samples (9/18, 50%), while showing excellent technical specificity in our sample set. We also confirmed the disappearance of all MRD signal with increasing time prior to relapse (>100 days), indicating true clinical specificity, even using genes commonly associated with clonal hematopoiesis of indeterminate potential (CHIP). This study highlights the efficacy of a highly sensitive, NGS panel-based approach to early detection of relapse in AML and supports the clinical validity of extending MRD analysis across many genes in the post-transplant setting.

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Section: Resultsmentioning

confidence: 95%

Measurable residual disease monitoring for patients with acute myeloid leukemia following hematopoietic cell transplantation using error corrected hybrid capture next generation sequencing

et al. 2019

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“…p-values Wilcoxon Two-sample test. Raw data extracted from GEO Datasets 151;152 D) CD34+CD38- cells from AML patient bone marrow (n=9) express higher levels of CEBPα, and a higher CEBPα/HOXB4 ratio, than CD34+CD38- cells from normal bone marrow (n=4) 150 . p-values Median Two-Sample test.…”

Section: Figurementioning

confidence: 99%

p53-Independent, Normal Stem Cell Sparing Epigenetic Differentiation Therapy for Myeloid and Other Malignancies

Saunthararajah

Triozzi

Rini

et al. 2012

Seminars in Oncology

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Summary Cytotoxic chemotherapy for acute myeloid leukemia (AML) usually produces only temporary remissions, at the cost of significant toxicity and risk for death. One fundamental reason for treatment failure is that it is designed to activate apoptosis genes (eg., TP53) that may be unavailable because of mutation or deletion. Unlike deletion of apoptosis genes, genes that mediate cell cycle exit by differentiation are present in myelodysplastic syndrome (MDS) and AML cells but are epigenetically repressed: MDS/AML cells express high levels of key lineage-specifying transcription factors (TF). Mutation in these TF (eg., CEBPA) or their cofactors (eg., RUNX1) affect transactivation function and produce epigenetic repression of late-differentiation genes that antagonize MYC. Importantly, this aberrant epigenetic repression can be redressed clinically by depleting DNA methyltransferase 1 (DNMT1, a central component of the epigenetic network that mediates transcription repression) using the deoxycytidine analogue decitabine (DAC) at non-cytotoxic concentrations. The DNMT1 depletion is sufficient to trigger upregulation of late-differentiation genes and irreversible cell cycle exit by p53-independent differentiation mechanisms. Fortuitously, the same treatment maintains or increases self-renewal of normal hematopoietic stem cells (HSC), which do not express high levels of lineage-specifying TF. The biological rationale for this approach to therapy appears to apply to cancers other than MDS/AML also. DAC or 5-azacytidine dose and schedule can be rationalized to emphasize this mechanism of action, as an alternative or complement to conventional apoptosis-based oncotherapy.

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“…According to the standard procedures [25], these cells were fractionated in terms of CD34 + expression, a marker of primitive hematopoietic cells. Before experiments, micro-beads were attached to the cell surface.…”

Section: B Experimental Preparationmentioning

confidence: 99%

Characterizing the micromechanical properties of myeloblasts from cancer patients with optical tweezers

Tan

Leung

Wang

et al. 2010

2010 IEEE International Conference on Nano/Molecular Medicine and Engineering

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Cell mechanics, in particular mechanical properties, has been suggested as a new biomarker indicative of cell state and phenotype. Acute myeloid leukemia (AML) is characterized by the abnormal increase of myeloblasts in blood and bone marrow. While AML has been extensively studied from the perspectives of biochemical and genetic aspects, little is known about its cellular biophysical properties. In this study, optical tweezer technology was used to examine the micromechanical properties of myeloblasts from bone marrow of AML patients at single cell level. The myeloblasts were separately analyzed according to their expression of CD34 + , a marker of primitive hematopoietic cells. To extract the intrinsic properties from the relationship between the stretching force and the induced deformation, a theoretical approach was developed to model the mechanical responses of cells and further characterize their mechanical properties. The preliminary results show that the area compressibility modulus of CD34 + myeloblasts was significantly less than that of CD34cells, which indicate that micromechanical properties are unique features of myeloblasts and provide us with an insight into the cell mechanics of primitive AML cells.

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A comparative study of bone marrow and peripheral blood CD34⁺ myeloblasts in acute myeloid leukaemia

Cited by 11 publications

References 46 publications

Measurable residual disease monitoring for patients with acute myeloid leukemia following hematopoietic cell transplantation using error corrected hybrid capture next generation sequencing

Measurable residual disease monitoring for patients with acute myeloid leukemia following hematopoietic cell transplantation using error corrected hybrid capture next generation sequencing

p53-Independent, Normal Stem Cell Sparing Epigenetic Differentiation Therapy for Myeloid and Other Malignancies

Characterizing the micromechanical properties of myeloblasts from cancer patients with optical tweezers

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A comparative study of bone marrow and peripheral blood CD34+ myeloblasts in acute myeloid leukaemia

Cited by 11 publications

References 46 publications

Measurable residual disease monitoring for patients with acute myeloid leukemia following hematopoietic cell transplantation using error corrected hybrid capture next generation sequencing

Measurable residual disease monitoring for patients with acute myeloid leukemia following hematopoietic cell transplantation using error corrected hybrid capture next generation sequencing

p53-Independent, Normal Stem Cell Sparing Epigenetic Differentiation Therapy for Myeloid and Other Malignancies

Characterizing the micromechanical properties of myeloblasts from cancer patients with optical tweezers

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A comparative study of bone marrow and peripheral blood CD34⁺ myeloblasts in acute myeloid leukaemia