CD14/16 monocyte profiling in juvenile myelomonocytic leukemia

Gadgeel, Manisha; Bagla, Shruti; Buck, Steven; Shamoun, Mark; Ravindranath, Yaddanapudi

doi:10.1002/pbc.28555

Cited by 6 publications

(2 citation statements)

References 22 publications

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“…tuberculosis and viral infections), there is an increase in the CD16 + subsets. On the other hand, monocyte CD16 expression is epigenetically reduced in myelodysplastic syndrome (MDS) and myeloproliferative neoplasms (MPNs) as in some cases of chronic myelomonocytic leukaemia (CMML) in adults and in some cahildren with RUNX1‐mutated MDS/MPN and juvenile myelomonocytic leukaemia (JMML) 32–34 . The finding of monocytopenia rather than monocytosis in our PN patients distinguishes them from this hypermethylated phenotype in MDS/MPN.…”

Section: Resultsmentioning

confidence: 69%

Defective monocyte plasticity and altered cAMP pathway characterize USB1‐mutated poikiloderma with neutropenia Clericuzio type

Parajuli,

Craig,

Gadgeel

et al. 2023

Br J Haematol

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SummaryPoikiloderma with neutropenia (PN) Clericuzio type (OMIM #604173) is a rare disease with areas of skin hyper‐ and hypopigmentation caused by biallelic USB1 variants. The current study was spurred by poor healing of a perianal tear wound in one affected child homozygous for c.266‐1G>A (p.E90Sfster8) mutation, from a family reported previously. Treatment with G‐CSF/CSF3 or GM‐CSF/CSF2 transiently increased neutrophil/monocytes count with no effect on wound healing. Analysis of peripheral blood revealed a lack of non‐classical (CD14+/−CD16+) monocytes, associated with a systemic inflammatory cytokine profile, in the two affected brothers. Importantly, despite normal expression of cognate receptors, monocytes from PN patients did not respond to M‐CSF or IL‐34 in vitro, as determined by cytokine secretion or CD16 expression. RNAseq of monocytes showed 293 differentially expressed genes, including significant downregulation of GATA2, AKAP6 and PDE4DIP that are associated with leucocyte differentiation and cyclic adenosine monophosphate (cAMP) signalling. Notably, the plasma cAMP was significantly low in the PN patients. Our study revealed a novel association of PN with a lack of non‐classical monocyte population. The defects in monocyte plasticity may contribute to disease manifestations in PN and a defective cAMP signalling may be the primary effect of the splicing errors caused by USB1 mutation.

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Section: Resultsmentioning

confidence: 69%

Defective monocyte plasticity and altered cAMP pathway characterize USB1‐mutated poikiloderma with neutropenia Clericuzio type

Parajuli,

Craig,

Gadgeel

et al. 2023

Br J Haematol

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“…[5][6][7] Leukoerythroblastosis is not part of the WHO criteria for diagnosis of JMML but is commonly seen on peripheral blood smear and recapitulates the myelodysplastic and myeloproliferative properties of this overlap syndrome. Flow cytometry is often helpful at diagnosis 8,9 to rule out other acute leukemias but does not play an important role thereafter unless the clinician is worried about progression to AML. Hyperphosphorylation of STAT5 was previously used as an adjunctive criterion for diagnosis but is not routinely offered in clinical laboratories.…”

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confidence: 99%

Juvenile myelomonocytic leukemia in the molecular era: a clinician’s guide to diagnosis, risk stratification, and treatment

et al. 2021

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Juvenile myelomonocytic leukemia is an overlapping myeloproliferative and myelodysplastic disorder of early childhood. It is associated with a spectrum of diverse outcomes ranging from spontaneous resolution in rare patients to transformation to acute myeloid leukemia in others that is generally fatal. This unpredictable clinical course, along with initially descriptive diagnostic criteria, led to decades of productive international research. Next generation sequencing now permits more accurate molecular diagnoses in nearly all patients. However, curative treatment is still reliant on allogeneic hematopoietic cell transplantation for most patients, and additional advances will be required to improve risk stratification algorithms that distinguish those that can be observed expectantly from others who require swift hematopoietic cell transplantation.

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Updates on germline predisposition in pediatric hematologic malignancies: What is the role of flow cytometry?

Demko,

Geyer

2024

Cytometry Part B Clinical

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Hematologic neoplasms with germline predisposition have been increasingly recognized as a distinct category of tumors over the last few years. As such, this category was added to the World Health Organization (WHO) 4th edition as well as maintained in the WHO 5th edition and International Consensus Classification (ICC) 2022 classification systems. In practice, these tumors require a high index of suspicion and confirmation by molecular testing. Flow cytometry is a cost‐effective diagnostic tool that is routinely performed on peripheral blood and bone marrow samples. In this review, we sought to summarize the current body of research correlating flow cytometric immunophenotype to assess its utility in diagnosis of and clinical decision making in germline hematologic neoplasms. We also illustrate these findings using cases mostly from our own institution. We review some of the more commonly mutated genes, including CEBPA, DDX41, RUNX1, ANKRD26, GATA2, Fanconi anemia, Noonan syndrome, and Down syndrome. We highlight that flow cytometry may have a role in the diagnosis (GATA2, Down syndrome) and screening (CEBPA) of some germline predisposition syndromes, although appears to show nonspecific findings in others (DDX41, RUNX1). In many of the others, such as ANKRD26, Fanconi anemia, and Noonan syndrome, further studies are needed to better understand whether specific flow cytometric patterns are observed. Ultimately, we conclude that further studies such as large case series and organized data pipelines are needed in most germline settings to better understand the flow cytometric immunophenotype of these neoplasms.

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CD14/16 monocyte profiling in juvenile myelomonocytic leukemia

Cited by 6 publications

References 22 publications

Defective monocyte plasticity and altered cAMP pathway characterize USB1‐mutated poikiloderma with neutropenia Clericuzio type

Defective monocyte plasticity and altered cAMP pathway characterize USB1‐mutated poikiloderma with neutropenia Clericuzio type

Juvenile myelomonocytic leukemia in the molecular era: a clinician’s guide to diagnosis, risk stratification, and treatment

Updates on germline predisposition in pediatric hematologic malignancies: What is the role of flow cytometry?

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