Abstract Chimeric antigen receptor (CAR) T cells have shown remarkable results in hematological malignancies but limited efficacy the setting of solid tumors. As myeloid-mediated immune suppression is known to play an important role dampening antitumor activity, we hypothesized that myeloid impact CAR cell expansion patients with A phase I trial (NCT02107963) was performed determine feasibility...

Acute myeloid leukemia (AML) is a type of poor prognosis hematological malignancies characterized by heterogeneous clonal expansion of myeloid progenitors. Leukemic stem cells are thought to form the majority of a cell population in minimal residual diseases (MRDs) which are resistant to current chemotherapeutic regimens and mediate disease relapse. Current therapeutic vaccine strategies have d...

PURPOSE Myeloid-derived suppressor cells (MDSC) have emerged as an immune-regulatory cell type that is expanded in tumor-bearing mice, but less is known about their immune-suppressive role in patients with cancer. EXPERIMENTAL DESIGN To study the importance of MDSC in patients with melanoma, we characterized the frequency, phenotype, and suppressive function of blood myeloid-derived cells and...

Myeloid/lymphoid neoplasms with FGFR1 rearrangement (MLN-FGFR1) comprise a heterogeneous group of that can present as myeloproliferative neoplasm, myelodysplastic/myeloproliferative acute myeloid leukemia, T or B lymphoblastic leukemia/lymphoma, mixed phenotype leukemia. The overall outcome these is poor, and patients often show cytogenetic evolution gain additional chromosomal abnormalities le...

Cancer-induced inflammation results in accumulation of myeloid cells. These myeloid cells include progenitors and progeny of monocytes, granulocytes, macrophages, and dendritic cells. It has become increasingly evident that tumor-dependent factors can condition myeloid cells toward an immunosuppressive and protumorigenic phenotype. Thus, myeloid cells are not simply bystanders in malignancy or ...

MicroRNAs are 19-24 nucleotides noncoding RNAs which silence modulate the expression of target genes by binding to the messenger RNAs. Myeloid malignancies include a broad spectrum of acute and chronic disorders originating from from the clonal transformation of a hematopoietic stem cell. Specific genetic abnormalities may define myeloid malignancies, such as translocation t(9;22) that represen...

The recent identification of DNMT3A mutations in de novo acute myeloid leukemia prompted us to determine their frequency, patterns and clinical impact in a cohort of 98 patients with either therapy-related or secondary acute myeloid leukemia developing from an antecedent hematologic disorder. We identified 24 somatic mutations in 23 patients with a significantly higher frequency in secondary ac...

GABP is an ets transcription factor that regulates genes that are required for myeloid differentiation. The tetrameric GABP complex includes GABPα, which binds DNA via its ets domain, and GABPβ, which contains the transcription activation domain. To examine the role of GABP in myeloid differentiation, we generated mice in which Gabpa can be conditionally deleted in hematopoietic tissues. Gabpa ...

Recruitment of innate immune cells from the bone marrow (BM) to an injury site is required for effective repair. In diabetes, this process is altered, leading to excessive recruitment and retention of dysfunctional myeloid cells that fail to promote angiogenesis, prolong inflammation, and block healing. The aberrant myeloid phenotype is partially mediated by stable intrinsic changes to developi...