List of antibodies for flow cytometry.

<div><p>Chronic myelomonocytic leukemia (CMML) is a rare blood cancer of older adults (3 in every 1,000,000 persons) characterized by poor survival and lacking effective mutation-specific therapy. Mutations in the ubiquitin ligase Cbl occur frequently in CMML and share biological and molecular features with a clonal disease occurring in children, juvenile myelomonocytic leukemia (JMML). Here we analyzed the clinical presentations, molecular features and immunophenotype of CMML patients with <i>CBL</i> mutations enrolled in a prospective Phase II clinical trial stratified according to molecular markers. Clinically, <i>CBL</i> mutations were associated with increased bone marrow blasts at diagnosis, leukocytosis and splenomegaly, similar to patients harboring <i>NRAS</i> or <i>KRAS</i> mutations. Interestingly, 64% of patients presented with more than one <i>CBL</i> variant implying a complex subclonal architecture, often with co-occurrence of <i>TET2</i> mutations. We found <i>CBL</i> mutations in CMML frequently clustered in the RING domain in contrast to JMML, where mutations frequently involve the linker helix region (<i>P</i><0.0001). According to our comparative alignment of available X-ray structures, mutations in the linker helix region such as Y371E give rise to conformational differences that could be exploited by targeted therapy approaches. Furthermore, we noted an increased percentage of CMML CD34<sup>+</sup> stem and progenitor cells expressing CD116 and CD131 in all <i>CBL</i> mutant cases and increased CD116 receptor density compared to healthy controls, similar to CMML overall. In summary, our data demonstrate that <i>CBL</i> mutations are associated with distinct molecular and clinical features in CMML and are potentially targetable with CD116-directed immunotherapy.</p></div>