Specific Skin Lesions in Chronic Myelomonocytic Leukemia: A Spectrum of Myelomonocytic and Dendritic Cell Proliferations. A Study of 42 Cases

2013 ◽  
Vol 2013 ◽  
pp. 102-103
Author(s):  
J. Wisell
2017 ◽  
Vol 44 (12) ◽  
pp. 1075-1079 ◽  
Author(s):  
Sanam Loghavi ◽  
Jonathan L. Curry ◽  
Guillermo Garcia-Manero ◽  
Keyur P. Patel ◽  
Jie Xu ◽  
...  

Leukemia ◽  
2017 ◽  
Vol 31 (5) ◽  
pp. 1238-1240 ◽  
Author(s):  
L Brunetti ◽  
V Di Battista ◽  
A Venanzi ◽  
G Schiavoni ◽  
M P Martelli ◽  
...  

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4344-4344
Author(s):  
Abhishek A. Mangaonkar ◽  
Kaaren K. Reichard ◽  
April Chiu ◽  
Matthew T Howard ◽  
Rebecca L King ◽  
...  

Abstract Introduction: Chronic myelomonocytic leukemia (CMML) is a chronic myeloid malignancy associated with monocytosis, autoimmunity (~30%) & an inherent risk for leukemic transformation. Bone marrow (BM) dendritic cell (DC) populations occur in ~30% of patients, with a poorly defined biological & prognostic role. The malignant immune microenvironment is regulated by indoleamine 2,3-dioxygenase-1 (IDO-1) expressing DCs, which modulate regulatory T (Treg) cells & block their conversion into proinflammatory T helper (Th17)-like cells. IDO-1 is a known immune checkpoint & functions by catabolizing tryptophan, an amino acid essential for T cell function. We hypothesized that distinct IDO-1 expressing DC populations in CMML modulate Tregs & contribute towards immune tolerance & aggressive disease biology. Methods: Primary diagnostic CMML peripheral blood mononuclear cells (PBMC) & BM biopsy specimens were obtained after Mayo Clinic IRB approval. A DC population was defined on H&E stained biopsy sections as focal collections (>10) of cells with characteristic elongated nuclei & cytoplasmic extensions. Transcriptomic & protein expression studies assessing IDO-1 expression were done by previously described methods. In addition, IHC expression of PD-1, PD-L1 & CTLA-4 was also done. IDO-1 promoter methylation studies with DIP-seq were performed. The impact on immune tolerance was assessed using mass cytometry (CyTOF). Results: Cohort: Twenty eight patients with CMML were included in the study, median age 70 (range: 51-80) years; 71% males. Eleven (39%) patients had coexisting autoimmune conditions. Of these, 8 (73%) had detectable DC populations either at diagnosis, or during the course of their disease. At a median follow-up of 46 (95% CI 27, 84) months, there were 14 (50%) deaths & 9 (32%) leukemic transformations.IHC results: Nine (32%) patients were identified to have a DC population at CMML diagnosis. CD123 & TCL1 staining was performed in 5 (56%) patients, with 3 being positive for both, & 2 positive for CD123 only (additional IHC studies ongoing). IDO1 expression by IHC was documented in all 9 (100%) cases (Fig 1A & 1B), while rare populations of PD-1, PD-L1 & CTLA-4 lymphocytes were also seen in all cases. Due to the low DC burdens (median cellularity ≤ 5%) & uniform staining intensity, IHC-based grading was not done. Samples at serial time-points, post-HMA therapy & at the time of blast transformation, were available in 5 & 3 patients respectively. Among the patients who did not have DC populations at diagnosis, 5 (42%) developed them post-HMA therapy, while 3 (50%) developed them at the time of LT. The development of DC populations was associated with loss of response to HMA (50%) & disease progression (50%).Transcriptomic analysis: RNA expression data was available on 7 (25%) patients, of whom only 1 (14%) had DC populations at diagnosis. The IDO-1 RPKM value in the former was higher than the mean pooled value in the latter group (330 versus 74, p=0.05).Methylation studies: DIP-seq was performed on 12 (43%) cases from the primary IHC cohort. Qualitative analysis of IDO-1 promoter hypomethylation was conducted & confirmed in all 9 (100%) cases with 5-mC & 5-hmC marks compared to input as displayed in figure 1C.Immune profiling: CyTOF was performed on 4 CMML samples (3 with IDO-1 expressing DC populations at diagnosis) from the primary IHC cohort & compared to a normal PBMC control. Results confirmed an increase in DC populations (fig 1D& 1E), & reduced % of Th17-like T cells in CMML samples compared to control (1.1 versus 5.07, p=0.05, fig 1F).Clinical correlates & survival analysis: With the exception that CMML patients with DC populations had a higher frequency of NRAS (P=0.007) mutations, the two groups were comparable for cytogenetic & molecular abnormalities. The median OS for the cohort was 45 (95% CI 29, 84) months. CMML patients with IDO-1 expressing DC populations at diagnosis had a shorter median OS, in comparison to those without (median OS 30 vs 45, p=0.03, Kaplan-Meier analysis in fig 1G). Conclusions: In conclusion, we demonstrate that DC populations are seen in ~30% of patients with CMML with a uniform expression of IDO-1 & limited expression of PD-1, PD-L1 & CTLA-4. CMML patients with BM DC populations have a higher frequency of NRAS mutations & DC IDO-1 expression is associated with tumor induced immune tolerance. Additional IHC, genomic & preclinical studies with IDO-1 inhibitors are ongoing. Figure 1. Figure 1. Disclosures Al-Kali: Novartis: Research Funding.


2021 ◽  
Vol 12 ◽  
Author(s):  
Grégoire Martin de Frémont ◽  
Pierre Hirsch ◽  
Santiago Gimenez de Mestral ◽  
Philippe Moguelet ◽  
Yoan Ditchi ◽  
...  

BackgroundMyelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) are associated with cutaneous manifestations. Next-generation sequencing (NGS) is a tool capable of identifying clonal myeloid cells in the skin infiltrate and thus better characterize the link between hematological diseases and skin lesions.ObjectiveTo assess whether skin lesions of MDS/CMML are clonally related to blood or bone marrow cells using NGS.MethodsComparisons of blood or bone marrow and skin samples NGS findings from patients presenting with MDS/CMML and skin lesions in three French hospitals.ResultsAmong the 14 patients recruited, 12 patients (86%) had mutations in the skin lesions biopsied, 12 patients (86%) had a globally similar mutational profile between blood/bone marrow and skin, and 10 patients (71%) had mutations with a high variant allele frequency (>10%) found in the myeloid skin infiltrate. Mutations in TET2 and DNMT3A, both in four patients, were the most frequent. Two patients harbored a UBA1 mutation on hematopoietic samples.LimitationsLimited number of patients and retrospective collection of the data. Blood and skin sampling were not performed at the exact same time point for two patients.ConclusionSkin lesions in the setting of MDS/CMML are characterized by a clonal myeloid infiltrate in most cases.


2020 ◽  
Vol 42 (11) ◽  
pp. 876-880 ◽  
Author(s):  
Angel Santos-Briz ◽  
Mario Medina-Miguelañez ◽  
David Moyano-Bueno ◽  
Alex Viñolas-Cuadros ◽  
Teresa G. Martínez ◽  
...  

Morphologia ◽  
2021 ◽  
Vol 14 (4) ◽  
pp. 49-57
Author(s):  
L. A. Pesotskaya ◽  
A. S. Korolenko

Background. Chronic myelomonocytic leukemia (CML) is rarely diagnosed and it is 1 per 100 thousand adults annually, in the United States - in 4 per million people, which is about 1100 cases per year. This disease is more common for men over 60. Results. A clinical case of a rare long-term course of myelodysplastic chronic myelomonocytic leukemia (MDCMML) in a middle-aged woman with rapid transformation into acute monocytic leukemia (AMoL-M5v) with atypical fulminant course is presented. Changes in the blood test were identified accidentally during a routine examination. A retrospective analysis of the course of the patient's disease, anamnesis made it possible to draw attention to the severe course of vasculitis of unknown etiology, with a predominant lesion of the skin of the lower limbs, which required inpatient treatment (19 years ago); skin lesions in the form of transient erythema, spotty eruptions for more than 10 years, moderate cervical lymphadenopathy. According to the WHO criteria, the morphological data of the bone marrow puncture corresponded to the MD of the CML. The long course of the disease without an obvious clinical picture, neutrophil dysplasia, myeloid proliferation was atypical, which did not exclude the presence of previous oligomonocytic CML in the patient. A detailed picture of the disease appeared after a viral infection, bronchitis, antibiotic therapy. In the absence of an increase in the number of blasts in the bone marrow, in a few of them normal Auer's sticks were detected, which, according to the literature, is a rarity in CML and an unfavorable prognostic factor of rapid transformation into acute myeloid leukemia. Conclusion. Not typical for the course of acute monocytic leukemia in this case were the absence of significant blastemia and severe suppression of normal hematopoiesis with pronounced extramedular manifestations. There was febrile fever, hyperplasia of the gums, tonsils with ulcerative-necrotic changes in the oral mucosa, an increase in cervical lymph nodes in the form of packets up to 2 cm in diameter with signs of sarcomatous growth. Attention was drawn to the progression of skin lesions, which was prognostically unfavorable. Notable was the development of severe hemorrhagic syndrome without severe thrombocytopenia, significant changes in the coagulogram, as a manifestation of early severe coagulopathy. There was a spread of erythematous elements on the skin with itching, not controlled by antihistamines and corticosteroid drugs (maculopapular rashes of a pink-cyanotic color, in places of a confluent nature, small-point hemorrhages like vasculitis over the entire surface of the skin).


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