By the same authors

From the same journal

From the same journal

The use of targeted sequencing and flow cytometry to identify patients with a clinically significant monocytosis

Research output: Contribution to journalArticle

Standard

The use of targeted sequencing and flow cytometry to identify patients with a clinically significant monocytosis. / Cargo, Catherine; Cullen, Matthew; Taylor, Jan; Short, Mike; Glover, Paul; Van Hoppe, Suzan; Smith, Alexandra Gwen; Evans, Paul; Crouch, Simon.

In: Blood, 03.01.2019.

Research output: Contribution to journalArticle

Harvard

Cargo, C, Cullen, M, Taylor, J, Short, M, Glover, P, Van Hoppe, S, Smith, AG, Evans, P & Crouch, S 2019, 'The use of targeted sequencing and flow cytometry to identify patients with a clinically significant monocytosis', Blood. https://doi.org/10.1182/blood-2018-08-867333

APA

Cargo, C., Cullen, M., Taylor, J., Short, M., Glover, P., Van Hoppe, S., ... Crouch, S. (2019). The use of targeted sequencing and flow cytometry to identify patients with a clinically significant monocytosis. Blood. https://doi.org/10.1182/blood-2018-08-867333

Vancouver

Cargo C, Cullen M, Taylor J, Short M, Glover P, Van Hoppe S et al. The use of targeted sequencing and flow cytometry to identify patients with a clinically significant monocytosis. Blood. 2019 Jan 3. https://doi.org/10.1182/blood-2018-08-867333

Author

Cargo, Catherine ; Cullen, Matthew ; Taylor, Jan ; Short, Mike ; Glover, Paul ; Van Hoppe, Suzan ; Smith, Alexandra Gwen ; Evans, Paul ; Crouch, Simon. / The use of targeted sequencing and flow cytometry to identify patients with a clinically significant monocytosis. In: Blood. 2019.

Bibtex - Download

@article{af5ad933974949f98210fe14b1096ef1,
title = "The use of targeted sequencing and flow cytometry to identify patients with a clinically significant monocytosis",
abstract = "The diagnosis of chronic myelomonocytic leukaemia (CMML) remains centred on morphology, meaning the distinction from a reactive monocytosis is challenging. Mutational analysis and immunophenotyping have been proposed as potential tools for diagnosis however have not been formally assessed in combination. We aimed to investigate the clinical utility of these technologies by performing targeted sequencing, in parallel to current gold standard techniques, on consecutive samples referred for investigation of monocytosis over a 2-year period (n=283). Results were correlated with the morphological diagnosis and objective outcome measures including overall survival (OS) and longitudinal blood counts. Somatic mutations were detected in 79{\%} of patients, being invariably identified in those with a confirmed diagnosis (99{\%}) though also in 57{\%} of patients with non-diagnostic BM features. The OS in non-diagnostic mutated patients was indistinguishable from those with CMML (p=0.118) and significantly worse than unmutated patients (p=0.0002). On multivariate analysis age, ASXL1, CBL, DNMT3A, NRAS & RUNX1 mutations retained significance. Furthermore, the presence of a mutation was associated with a progressive fall in haemoglobin/platelet levels and increasing monocyte counts compared with mutation negative patients. Of note, the immunophenotypic features of non-diagnostic mutated patients were comparable to CMML patients and the presence of aberrant CD56 was highly specific for detecting a mutation. Overall, somatic mutations are detected at high frequency in patients referred with a monocytosis irrespective of diagnosis. In those without a WHO defined diagnosis, the mutation spectrum, immunophenotypic features and OS are indistinguishable from CMML patients and these patients should be managed as such.",
author = "Catherine Cargo and Matthew Cullen and Jan Taylor and Mike Short and Paul Glover and {Van Hoppe}, Suzan and Smith, {Alexandra Gwen} and Paul Evans and Simon Crouch",
note = "{\circledC} 2019, American Society of Hematology. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details.",
year = "2019",
month = "1",
day = "3",
doi = "10.1182/blood-2018-08-867333",
language = "English",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - The use of targeted sequencing and flow cytometry to identify patients with a clinically significant monocytosis

AU - Cargo, Catherine

AU - Cullen, Matthew

AU - Taylor, Jan

AU - Short, Mike

AU - Glover, Paul

AU - Van Hoppe, Suzan

AU - Smith, Alexandra Gwen

AU - Evans, Paul

AU - Crouch, Simon

N1 - © 2019, American Society of Hematology. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details.

PY - 2019/1/3

Y1 - 2019/1/3

N2 - The diagnosis of chronic myelomonocytic leukaemia (CMML) remains centred on morphology, meaning the distinction from a reactive monocytosis is challenging. Mutational analysis and immunophenotyping have been proposed as potential tools for diagnosis however have not been formally assessed in combination. We aimed to investigate the clinical utility of these technologies by performing targeted sequencing, in parallel to current gold standard techniques, on consecutive samples referred for investigation of monocytosis over a 2-year period (n=283). Results were correlated with the morphological diagnosis and objective outcome measures including overall survival (OS) and longitudinal blood counts. Somatic mutations were detected in 79% of patients, being invariably identified in those with a confirmed diagnosis (99%) though also in 57% of patients with non-diagnostic BM features. The OS in non-diagnostic mutated patients was indistinguishable from those with CMML (p=0.118) and significantly worse than unmutated patients (p=0.0002). On multivariate analysis age, ASXL1, CBL, DNMT3A, NRAS & RUNX1 mutations retained significance. Furthermore, the presence of a mutation was associated with a progressive fall in haemoglobin/platelet levels and increasing monocyte counts compared with mutation negative patients. Of note, the immunophenotypic features of non-diagnostic mutated patients were comparable to CMML patients and the presence of aberrant CD56 was highly specific for detecting a mutation. Overall, somatic mutations are detected at high frequency in patients referred with a monocytosis irrespective of diagnosis. In those without a WHO defined diagnosis, the mutation spectrum, immunophenotypic features and OS are indistinguishable from CMML patients and these patients should be managed as such.

AB - The diagnosis of chronic myelomonocytic leukaemia (CMML) remains centred on morphology, meaning the distinction from a reactive monocytosis is challenging. Mutational analysis and immunophenotyping have been proposed as potential tools for diagnosis however have not been formally assessed in combination. We aimed to investigate the clinical utility of these technologies by performing targeted sequencing, in parallel to current gold standard techniques, on consecutive samples referred for investigation of monocytosis over a 2-year period (n=283). Results were correlated with the morphological diagnosis and objective outcome measures including overall survival (OS) and longitudinal blood counts. Somatic mutations were detected in 79% of patients, being invariably identified in those with a confirmed diagnosis (99%) though also in 57% of patients with non-diagnostic BM features. The OS in non-diagnostic mutated patients was indistinguishable from those with CMML (p=0.118) and significantly worse than unmutated patients (p=0.0002). On multivariate analysis age, ASXL1, CBL, DNMT3A, NRAS & RUNX1 mutations retained significance. Furthermore, the presence of a mutation was associated with a progressive fall in haemoglobin/platelet levels and increasing monocyte counts compared with mutation negative patients. Of note, the immunophenotypic features of non-diagnostic mutated patients were comparable to CMML patients and the presence of aberrant CD56 was highly specific for detecting a mutation. Overall, somatic mutations are detected at high frequency in patients referred with a monocytosis irrespective of diagnosis. In those without a WHO defined diagnosis, the mutation spectrum, immunophenotypic features and OS are indistinguishable from CMML patients and these patients should be managed as such.

U2 - 10.1182/blood-2018-08-867333

DO - 10.1182/blood-2018-08-867333

M3 - Article

JO - Blood

JF - Blood

SN - 0006-4971

ER -