Granulomatous dermatitis in the context of chronic myelomonocytic leukemia: More than just reactive infiltrates. An illustrative case report with literature review.

Traditionally, skin involvement in chronic myelomonocytic leukemia (CMML) has been considered to be either specific (leukemia cutis) or non-specific, with granulomatous dermatitis included in the latter group. More recently, the true nature of the myeloid cells present in the cutaneous infiltrates of this theoretically reactive dermatitis is being clarified with the use of new molecular techniques such as next-generation sequencing. The same mutations in bone marrow (BM) myeloid neoplastic cells and in the cells of cutaneous infiltrates have been found.

Dinaciclib synergizes with BH3 mimetics targeting BCL-2 and BCL-X in multiple myeloma cell lines partially dependent on MCL-1 and in plasma cells from patients.

A better understanding of multiple myeloma (MM) biology has led to the development of novel therapies. However, MM is still an incurable disease and new pharmacological strategies are needed. Dinaciclib, a multiple cyclin-dependent kinase (CDK) inhibitor, which inhibits CDK1, 2, 5 and 9, displays significant antimyeloma activity as found in phase II clinical trials.

Ecto-calreticulin expression in multiple myeloma correlates with a failed anti-tumoral immune response and bad prognosis.

Immunogenic cell death (ICD) has been proposed to be a crucial process for antitumor immunosurveillance. ICD is characterized by the exposure and emission of Damage Associated Molecular Patterns (DAMP), including calreticulin (CRT). A positive correlation between CRT exposure or total expression and improved anticancer immunosurveillance has been found in certain cancers, usually accompanied by favorable patient prognosis.

Granulomatous Dermatitis Heralding Myelodisplastic/Myeloproliferative Neoplasms. Neoplastic or Reactive Cells? A Study of 2 Cases.

Skin manifestations in the context of underlying hematological malignancies are well known and not an infrequent clinical finding. They can represent specific neoplastic infiltrates or be considered as reactive. In the latter group, where granulomatous dermatitis is included, controversy has emerged recently.

Harnessing the Potential of NK Cell-Based Immunotherapies against Multiple Myeloma.

Natural killer (NK) cell-based therapies have emerged as promising anticancer treatments due to their potency as cytolytic effectors and synergy with concurrent treatments. Multiple myeloma (MM) is an aggressive B-cell malignancy that, despite development of novel therapeutic agents, remains incurable with a high rate of relapse. In MM, the inhospitable tumor microenvironment prevents host NK cells from exerting their cytolytic function.

Expanded NK cells from umbilical cord blood and adult peripheral blood combined with daratumumab are effective against tumor cells from multiple myeloma patients.

In this study we evaluated the potential of expanded NK cells (eNKs) from two sources combined with the mAbs daratumumab and pembrolizumab to target primary multiple myeloma (MM) cells . In order to ascertain the best source of NK cells, we expanded and activated NK cells from peripheral blood (PB) of healthy adult donors and from umbilical cord blood (UCB). The resulting expanded NK (eNK) cells express CD16, necessary for carrying out antibody-dependent cellular cytotoxicity (ADCC).

Expanded and activated allogeneic NK cells are cytotoxic against B-chronic lymphocytic leukemia (B-CLL) cells with sporadic cases of resistance.

Adoptive transfer of allogeneic natural killer (NK) cells is becoming a credible immunotherapy for hematological malignancies. In the present work, using an optimized expansion/activation protocol of human NK cells, we generate expanded NK cells (eNK) with increased expression of CD56 and NKp44, while maintaining that of CD16. These eNK cells exerted significant cytotoxicity against cells from 34 B-CLL patients, with only 1 sample exhibiting resistance.

Activated Allogeneic NK Cells Preferentially Kill Poor Prognosis B-Cell Chronic Lymphocytic Leukemia Cells.

Mutational status of together with expression of wild-type (wt) represents the most widely accepted biomarkers, establishing a very poor prognosis in B-cell chronic lymphocytic leukemia (B-CLL) patients. Adoptive cell therapy using allogeneic HLA-mismatched Natural killer (NK) cells has emerged as an effective and safe alternative in the treatment of acute myeloid and lymphoid leukemias that do not respond to traditional therapies. We have described that allogeneic activated NK cells eliminate hematological cancer cell lines with multidrug resistance acquired by mutations in the apoptotic machinery.

Prognostic impact of chromosomal translocations in myelodysplastic syndromes and chronic myelomonocytic leukemia patients. A study by the spanish group of myelodysplastic syndromes.

Chromosomal translocations are rare in the myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). With the exception of t(3q), translocations are not explicitly considered in the cytogenetic classification of the IPSS-R and their impact on disease progression and patient survival is unknown. The present study was aimed at determining the prognostic impact of translocations in the context of the cytogenetic classification of the IPSS-R.

Refining the Breakpoints of Three New Translocations Identified in Myelodysplastic Syndromes.

Recurrent translocations are uncommon in myelodysplastic syndromes (MDS). Three new recurrent translocations, namely der(12)t(3;12)(q13;p13), t(11;13;22)(q13;q14;q12) and der(17)t(13;17)(q21;p13), identified by conventional cytogenetics (CC) in 4 MDS patients, were further characterized using a panel of commercial and homemade fluorescence in situ hybridization (FISH) probes. The goal of this study was to determine the precise breakpoints and to identify genes that could be related with the neoplastic process.

Human NK cells activated by EBV lymphoblastoid cells overcome anti-apoptotic mechanisms of drug resistance in haematological cancer cells.

Natural killer (NK) cells recognize and eliminate transformed or infected cells that have downregulated MHC class-I and express specific activating ligands. Recent evidence indicates that allogeneic NK cells are useful to eliminate haematological cancer cells independently of MHC-I expression. However, it is unclear if transformed cells expressing mutations that confer anti-apoptotic properties and chemoresistance will be susceptible to NK cells.

Multivariate time-dependent comparison of the impact of lenalidomide in lower-risk myelodysplastic syndromes with chromosome 5q deletion.

The impact of lenalidomide treatment on long-term outcomes of patients with lower risk myelodysplastic syndromes (MDS) and chromosome 5q deletion (del(5q)) is unclear. This study used time-dependent multivariate methodology to analyse the influence of lenalidomide therapy on overall survival (OS) and acute myeloblastic leukaemia (AML) progression in 215 patients with International Prognostic Scoring System (IPSS) low or intermediate-1 risk and del(5q). There were significant differences in several relevant characteristics at presentation between patients receiving (n = 86) or not receiving lenalidomide (n = 129).

Transfusion dependence development and disease evolution in patients with MDS and del(5q) and without transfusion needs at diagnosis.

Patients with isolated del(5q) and MDS are considered to have good prognosis as compared to other MDS subtypes. Most patients suffered of anemia and 50% of them required transfusions at diagnosis. It is known that for patients with MDS and del(5q) in transfusion dependence(TD), Lenalidomide is the first choice treatment.

Granulysin induces apoptotic cell death and cleavage of the autophagy regulator Atg5 in human hematological tumors.

Granulysin is a protein present in the granules of human CTL and NK cells, with cytolytic activity against microbes and tumors. Previous work demonstrated that granulysin caused cell death through mitochondrial damage with release of AIF and cytochrome c. However, the molecular mechanism and, especially, the type of cell death were still not well defined.

Reciprocal translocations in myelodysplastic syndromes and chronic myelomonocytic leukemias: review of 5,654 patients with an evaluable karyotype.

The infrequency of translocations in myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemias (CMML) makes their identification and reporting interesting for the recognition of the recurrent ones and the genes involved in these neoplasias. The aims of this study were to identify new translocations associated with MDS and CMML and to establish their frequency in a cohort of 8,016 patients from the Spanish Group of MDS database. The karyotype was evaluable in 5,654 (70%) patients.

Iminophosphorane-organogold(III) complexes induce cell death through mitochondrial ROS production.

Gold compounds are being investigated as potential antitumor drugs. Some gold(III) derivatives have been shown to induce cell death in solid tumors but their mechanism of action differs from that of cisplatin, since most of these compounds do not bind to DNA. We have explored cellular events triggered by three different iminophosphorane-organogold(III) compounds in leukemia cells (a neutral compound with two chloride ligands [Au{κ(2)-C,N-C(6)H(4)(PPh(2)=N(C(6)H(5))-2}Cl(2)] 1, and two cationic compounds with either a dithiocarbamate ligand [Au{κ(2)-C,N-C(6)H(4)(PPh(2)=N(C(6)H(5))-2}(S(2)CN-Me(2))]PF(6)2, or a water-soluble phosphine and a chloride ligand [Au{κ(2)-C,N-C(6)H(4)(PPh(2)=N(C(6)H(5))-2}(P{Cp(m-C(6)H(4)-SO(3)Na)(2)}(3)) Cl]PF(6)3).