Monocyte subset analysis accurately distinguishes CMML from MDS and is associated with a favorable MDS prognosis

Talati, Chetasi; Zhang, Ling; Shaheen, Ghada; Kuykendall, Andrew; Ball, Markus; Zhang, Qing; Lancet, Jeffrey E.; Zuckerman, Kenneth S.; List, Alan F.; Komrokji, Rami; Moscinski, Lynn C.; Padron, Eric

doi:10.1182/blood-2016-12-753210

Cited by 61 publications

(78 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…2 Subsequent studies have validated these findings and also confirmed the ability to distinguish CMML from MDS and myeloproliferative neoplasm cases presenting with a monocytosis. 21,22 However, these studies are centered on morphological diagnoses, and mutational analyses have not been performed consistently. Although our study has shown a strong correlation between skewed monocyte subsets and a diagnosis of CMML, this did not capture all patients and was neither sensitive nor specific for the presence of a mutation.…”

Section: Discussionmentioning

confidence: 99%

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

Cargo

Cullen

Taylor

et al. 2019

Blood

View full text Add to dashboard Cite

The diagnosis of chronic myelomonocytic leukemia (CMML) remains centered on morphology, meaning that the distinction from a reactive monocytosis is challenging. Mutational analysis and immunophenotyping have been proposed as potential tools for diagnosis; however, they have not been formally assessed in combination. We aimed to investigate the clinical utility of these technologies by performing targeted sequencing, in parallel with 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%) but also in 57% of patients with nondiagnostic bone marrow features. The OS in nondiagnostic mutated patients was indistinguishable from those with CMML (P = .118) and significantly worse than in unmutated patients (P = .0002). On multivariate analysis, age, ASXL1, CBL, DNMT3A, NRAS, and RUNX1 mutations retained significance. Furthermore, the presence of a mutation was associated with a progressive decrease in hemoglobin/platelet levels and increasing monocyte counts compared with mutation-negative patients. Of note, the immunophenotypic features of nondiagnostic 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 World Health Organization–defined diagnosis, the mutation spectrum, immunophenotypic features, and OS are indistinguishable from CMML patients, and these patients should be managed as such.

show abstract

Section: Discussionmentioning

confidence: 99%

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

Cargo

Cullen

Taylor

et al. 2019

Blood

View full text Add to dashboard Cite

show abstract

“…Importantly, this repartition was noted to be independent of CMML mutational status, and this increment corrected in CMML patients that responded to hypomethylating agents (HMA) . This technique has also been used to effectively distinguish monocytosis associated with CMML from monocytosis seen in patients with MPN, and in identifying MDS patients with monocyte counts <1 × 10 9 /L who eventually develop CMML . False negatives with this technique have been encountered in CMML patients with autoimmune diseases where the MO2 fraction increases (false decrease in MO1), and in other myeloid malignancies such as CML and atypical CML .…”

Section: Diagnosismentioning

confidence: 99%

“…This technique has also been used to effectively distinguish monocytosis associated with CMML from monocytosis seen in patients with MPN, and in identifying MDS patients with monocyte counts <1 × 10 9 /L who eventually develop CMML . False negatives with this technique have been encountered in CMML patients with autoimmune diseases where the MO2 fraction increases (false decrease in MO1), and in other myeloid malignancies such as CML and atypical CML . We hope that by using additional monocyte markers such as CCR2, CD36, HLA‐DR and CD11c, and better assessment techniques such as mass cytometry (cytometry by time of flight‐CyTOF), we can improve upon the sensitivity and specificity of this methodology…”

Section: Diagnosismentioning

confidence: 99%

Chronic Myelomonocytic leukemia: 2020 update on diagnosis, risk stratification and management

2019

View full text Add to dashboard Cite

Disease overview: Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder with overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms, with an inherent risk for leukemic transformation (~15% over 3-5 years). Diagnosis: Diagnosis is based on the presence of sustained (>3 months) peripheral blood monocytosis (≥1 × 10 9 /L; monocytes ≥10%), along with bone marrow dysplasia. Clonal cytogenetic abnormalities occur in~30% of patients, while >90% have gene mutations. Mutations involving TET2 (~60%), SRSF2 (~50%), ASXL1 (~40%) and the oncogenic RAS pathway (~30%) are frequent; while the presence of ASXL1 and DNMT3A mutations and the absence of TET2 mutations negatively impact over-all survival. Risk stratification: Molecularly integrated prognostic models include; the Groupe Français des Myélodysplasies (GFM), Mayo Molecular Model (MMM) and the CMML specific prognostic model (CPSS-Mol). Risk factors incorporated into the MMM include presence of nonsense or frameshift ASXL1 mutations, absolute monocyte count>10 × 10 9 /L, hemoglobin <10 g/dL, platelet count <100 × 10 9 /L and the presence of circulating immature myeloid cells. The MMM stratifies CMML patients into four groups; high (≥3 risk factors), intermediate-2 (2 risk factors), intermediate-1 (1 risk factor) and low (no risk factors), with median survivals of 16, 31, 59 and 97 months, respectively.Risk-adapted therapy: Hypomethylating agents such as 5-azacitidine and decitabine are commonly used, with overall response rates of~40%-50% and complete remission rates of~7%-17%; with no impact on mutational allele burdens. Allogeneic stem cell transplant is the only potentially curative option, but is associated with significant morbidity and mortality.

show abstract

“…The latter can be used as a diagnostic tool. Selimoglu-Buet et al [17] showed that using a cut-off of > 94% classical monocytes, discriminates CMML from reactive monocytosis with a specificity of 95.1% and a sensitivity of 91.9% [17][18][19][20].…”

Section: The Maturing Myelomonocytic Lineagementioning

confidence: 99%

Clinical Implication of Multi-Parameter Flow Cytometry in Myelodysplastic Syndromes

Duetz¹,

Westers²,

Loosdrecht

2018

Pathobiology

View full text Add to dashboard Cite

Myelodysplastic syndromes (MDS) are a challenging group of diseases for clinicians and researchers, as both disease course and pathobiology are highly heterogeneous. In (suspected) MDS patients, multi-parameter flow cytometry can aid in establishing diagnosis, risk stratification and choice of therapy. This review addresses the developments and future directions of multi-parameter flow cytometry scores in MDS. Additionally, we propose an integrated diagnostic algorithm for suspected MDS.

show abstract

Monocyte subset analysis accurately distinguishes CMML from MDS and is associated with a favorable MDS prognosis

Cited by 61 publications

References 5 publications

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

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

Chronic Myelomonocytic leukemia: 2020 update on diagnosis, risk stratification and management

Clinical Implication of Multi-Parameter Flow Cytometry in Myelodysplastic Syndromes

Contact Info

Product

Resources

About