Diagnostic criteria for juvenile myelomonocytic leukemia (JMML) are currently well defined, however in some patients diagnosis still remains a challenge. Flow cytometry is a well established tool for diagnosis and follow-up of hematological malignancies, nevertheless it is not routinely used for JMML diagnosis. Herewith, we characterized the CD34+ hematopoietic precursor cells collected from 31 children with JMML using a combination of standardized EuroFlow antibody panels to assess the ability to discriminate JMML cells from normal/reactive bone marrow cell as controls (n=29) or from cells of children with other hematological diseases mimicking JMML (n=9). CD34+ precursors in JMML showed markedly reduced B-cell and erythroid-committed precursors compared to controls, whereas monocytic and CD7+ lymphoid precursors were significantly expanded. Moreover, aberrant immunophenotypes were consistently present in CD34+ precursors in JMML, while they were virtually absent in controls. Multivariate logistic regression analysis showed that combined assessment of the number of CD34+CD7+ lymphoid precursors and CD34+ aberrant precursors or erythroid precursors had a great potential in discriminating JMMLs versus controls. Importantly our scoring model allowed highly efficient discrimination of truly JMML versus patients with JMML-like diseases. In conclusion, we show for the first time that CD34+ precursors from JMML patients display a unique immunophenotypic profile which might contribute to a fast and accurate diagnosis of JMML worldwide by applying an easy to standardize single eight-color antibody combination.

• MeSH
• antigeny CD34 genetika   MeSH
• dítě MeSH
• juvenilní myelomonocytární leukemie * diagnóza   genetika   MeSH
• lidé MeSH
• monocyty patologie   MeSH
• průtoková cytometrie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny CD34 MeSH

Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative disorder of early childhood characterized by mutations activating RAS signaling. Established clinical and genetic markers fail to fully recapitulate the clinical and biological heterogeneity of this disease. Here we report DNA methylome analysis and mutation profiling of 167 JMML samples. We identify three JMML subgroups with unique molecular and clinical characteristics. The high methylation group (HM) is characterized by somatic PTPN11 mutations and poor clinical outcome. The low methylation group is enriched for somatic NRAS and CBL mutations, as well as for Noonan patients, and has a good prognosis. The intermediate methylation group (IM) shows enrichment for monosomy 7 and somatic KRAS mutations. Hypermethylation is associated with repressed chromatin, genes regulated by RAS signaling, frequent co-occurrence of RAS pathway mutations and upregulation of DNMT1 and DNMT3B, suggesting a link between activation of the DNA methylation machinery and mutational patterns in JMML.

• MeSH
• biopsie MeSH
• chromatin genetika   metabolismus   MeSH
• dítě MeSH
• DNA-(cytosin-5-)methyltransferasa metabolismus   MeSH
• DNA-(cytosin-5)-methyltransferasa 1 metabolismus   MeSH
• DNA-methyltransferasa 3B MeSH
• epigenomika MeSH
• juvenilní myelomonocytární leukemie genetika   mortalita   patologie   terapie   MeSH
• kojenec MeSH
• lidé MeSH
• metylace DNA * MeSH
• mutace MeSH
• mutační analýza DNA MeSH
• Noonanové syndrom genetika   patologie   MeSH
• předškolní dítě MeSH
• prognóza MeSH
• prospektivní studie MeSH
• protinádorové látky terapeutické užití   MeSH
• protoonkogenní proteiny c-cbl MeSH
• protoonkogenní proteiny p21(ras) genetika   metabolismus   MeSH
• regulace genové exprese u leukemie MeSH
• signální transdukce genetika   MeSH
• transplantace hematopoetických kmenových buněk MeSH
• tyrosinfosfatasa nereceptorového typu 11 genetika   metabolismus   MeSH
• upregulace MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chromatin MeSH
• DNA-(cytosin-5-)methyltransferasa MeSH
• DNA-(cytosin-5)-methyltransferasa 1 MeSH
• DNMT1 protein, human MeSH Prohlížeč
• KRAS protein, human MeSH Prohlížeč
• protinádorové látky MeSH
• protoonkogenní proteiny c-cbl MeSH
• protoonkogenní proteiny p21(ras) MeSH
• PTPN11 protein, human MeSH Prohlížeč
• tyrosinfosfatasa nereceptorového typu 11 MeSH