Correlation between peripheral blood and bone marrow regarding FLT3-ITD and NPM1 mutational status in patients with acute myeloid leukemia

Tong, Wei; Sandhu, Vicky; Wood, Brent L.; Hendrie, Paul C.; Becker, Pamela S.; Pagel, John M.; Walter, Roland B.; Estey, Elihu H.

doi:10.3324/haematol.2014.118422

Cited by 16 publications

(8 citation statements)

References 11 publications

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“…Molecular analysis has similarly been compared between peripheral blood and bone marrow samples, and peripheral blood has high sensitivity and specificity for detection of FLT3 -ITD and NPM1 mutations when the blast count is >2000 cells per microliter. 16,17 More recently, the protein expression pattern (so-called proteome) has been shown to be closely correlated between peripheral blood and bone marrow blasts, though this finding is not clinically relevant at the current time. 18 …”

Section: Use Of Marrow In Initial Diagnosismentioning

confidence: 86%

Bone marrow evaluation for diagnosis and monitoring of acute myeloid leukemia

et al. 2017

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The diagnosis of acute myeloid leukemia (AML) can be made based on peripheral blood or bone marrow blasts. In this review, we will discuss the role of bone marrow evaluation and peripheral blood monitoring in the diagnosis, management, and follow up of AML patients. For patients with circulating blasts, it is reasonable to perform the necessary studies needed for diagnosis and risk stratification, including multiparametric flow cytometry, cytogenetics, and molecular analysis, on a peripheral blood specimen. The day 14 marrow is used to document hypocellularity in response to induction chemotherapy, but it is unclear if that assessmentis necessary as it often does not affect immediate management. Currently, response assessments performed at count recovery for evaluation of remission and measurable residual disease rely on bone marrow sampling. For monitoring of relapse, peripheral blood evaluation may be adequate, but the sensitivity of bone marrow testing is in some cases superior. While bone marrow evaluation can certainly be avoided in particular situations, this cumbersome and uncomfortable procedure currently remains the de facto standard for response assessment.

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Section: Use Of Marrow In Initial Diagnosismentioning

confidence: 86%

Bone marrow evaluation for diagnosis and monitoring of acute myeloid leukemia

et al. 2017

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“…10 Other groups have observed concordant PB NPM1 mutation clearance and PB copy number abnormalities [11][12][13][14] and have occasionally used PB for mutation discovery. [15][16][17] Therefore, we sought to compare the mutation burden in paired serial PB and BM samples in patients with AML or MDS to determine whether sequencing of PB samples is a viable approach for determining clonal architecture and whether it might provide an adjunct, and less invasive, measure of response to therapy.…”

mentioning

confidence: 99%

Mutational landscape and response are conserved in peripheral blood of AML and MDS patients during decitabine therapy

Duncavage¹,

Uy²,

Petti

et al. 2017

Blood

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“…The extent and timing of engraftment varied considerably, as illustrated by the plot of baseline bone marrow counts in Figure 1D. Furthermore, the distribution of the cells (PB, BM, spleen) also varied markedly, suggesting that in some cases the number of PB cells can underestimate the overall disease burden (Figure 1E), despite their reported fidelity in mimicking disease in terms of their mutational profile (14). In 7 of 16 successful engraftments, the bone marrow and spleen were the predominate sites of engraftment (Table II), which is typical of AML PDX modeling (15).…”

Section: Resultsmentioning

confidence: 99%

Co-clinical Modeling of the Activity of the BET Inhibitor Mivebresib (ABBV-075) in AML

Albert

Goodwin

Davies

et al. 2022

In Vivo

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Background/Aim: The therapeutic potential of bromodomain and extra-terminal motif (BET) inhibitors in hematological cancers has been well established in preclinical and early-stage clinical trials, although as of yet, no BETtargeting agent has achieved approval. To add insight into potential response to mivebresib (ABBV-075), a broadspectrum BET inhibitor, co-clinical modeling of individual patient biopsies was conducted in the context of a Phase I trial in acute myeloid leukemia (AML). Materials and Methods: Coclinical modeling involves taking the patient's biopsy and implanting it in mice with limited passage so that it closely retains the original characteristics of the malignancy and allows comparisons of response between animal model and clinical data. Procedures were developed, initially with neonate NOD/Shi-scid-IL2rγnull (NOG) mice and then optimized with juvenile NOG-EXL as host mice, eventually resulting in a robust rate of engraftment (16 out of 26, 62%). Results: Results from the co-clinical AML patient-derived xenograft (PDX) modeling (6 with >60% inhibition of bone marrow blasts) were consistent with the equivalent clinical data from patients receiving mivebresib in monotherapy, and in combination withvenetoclax. The modeling system also demonstrated the activity of a novel BD2-selective BET inhibitor (ABBV-744) in the preclinical AML setting. Both agents were also highly effective in inhibiting blast counts in the spleen (10/10 and 5/6 models, respectively). Conclusion: These findings confirm the validity of the model system in the co-clinical setting, establish highly relevant in vivo models for the discovery of cancer therapy, and indicate the therapeutic value of BET inhibitors for AML and, potentially, myelofibrosis treatment.Mivebresib is a broad-spectrum, highly potent bromodomain and extra-terminal motif (BET) inhibitor with a promising preclinical profile in solid and hematological cancers (1-6). Preclinically, mivebresib induces strong apoptosis in cell 1615

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Correlation between peripheral blood and bone marrow regarding FLT3-ITD and NPM1 mutational status in patients with acute myeloid leukemia

Cited by 16 publications

References 11 publications

Bone marrow evaluation for diagnosis and monitoring of acute myeloid leukemia

Bone marrow evaluation for diagnosis and monitoring of acute myeloid leukemia

Mutational landscape and response are conserved in peripheral blood of AML and MDS patients during decitabine therapy

Co-clinical Modeling of the Activity of the BET Inhibitor Mivebresib (ABBV-075) in AML

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