Journal of Clinical Haematology

Flavopiridol (FVP; alvocidib), an FDA-approved orphan drug, has been studied in clinical trials under both single treatment and combination scenarios; several singleagent Phase I and Phase II clinical trials against leukemia, lymphomas, and solid tumors are active. To date, there have been more than 50 clinical trials involving FVP in the United States. Unfortunately, almost half of patients on FVP clinical trials showed serious adverse effects, implicating appropriate dosages need to be found and an alternative way to circumvent the toxicity of FVP with synergistic agents.

Extracellular vesicles (EVs) are emerging as a key mediator of intercellular communication as well as a major mechanism of functional reprogramming of cells in disease. All cells produce EVs, which freely circulate and are found in all body fluids. EVs are heterogenous, consisting of subsets of vesicles with different sizes, distinct origins, and various functions (Figure 1). They mediate a broad variety of biological events ranging from cellular activation, inflammation, blood coagulation, angiogenesis, cellular transport, and others. Among these vesicles, a subset of small EVs (30-150 nm in diameter) originating from multivesicular bodies (MVBs) in parent cells and referred to as small extracellular vesicles (sEVs) carry proteomic, genomic and functional signatures that resemble those of parent cells and are, therefore, taken as surrogates of parent cells. In cancer, tumor-derived exosomes (TEX) reflect characteristics of tumor cells and are considered candidates for “liquid tumor biopsy”. Emerging evidence shows that TEX are a major sEV subset in plasma of patients with cancer, including hematologic malignancies.

Platelet preparations (PDPs) have gained success, mainly due to their high concentrations of biologically active molecules, such as growth factors and cytokines, which play an important role in tissue repair and reconstruction. Recent knowledge shows that platelets can play a new role in tissue reproduction and vascular restoration, as well as being the protagonists of inflammatory processes and immune system responses. They release bio-active proteins and other active ingredients that can affect a number of phenomena that promote cell consumption, growth and transformation (growth factors).

Breast cancer is the most frequent malignancy in females. Due to its major impact on the population, this disease represents a critical public health problem that requires further research at the molecular level to define its prognosis and specific treatment. Basic research is required to accomplish this task and this involves cell lines as they can be widely used in many aspects of laboratory research and, particularly, as in vitro models in cancer research. MCF-7 is a commonly used breast cancer cell line, that has been promoted for more than 40 years by multiple research groups but its characteristics have never been gathered in a consistent review article. 

COVID-19 has challenged global health and affected many countries. The disease had infected more than 16 million people and killed over 650,000 ones by the end of July 2020. According to Sahu et al., COVID-19 epidemic is the third most common coronavirus in the 21st century, resulting in numerous deaths all over the world. It has caused severe psychological stress and increased hospital visits along with increased tiredness and burnout of medical staff. The disease has also raised many problems for the management of hospitals and diagnostic-treatment centers, so that many of them have no capacity to receive patients.

Leukemia is a tumor of the primary blood-forming cells. leukemia is not only a cancer of the white blood cells but also it originates in other blood cell types. Types of leukemia are categorized based on the rate of growth to acute (fastgrowing) or chronic (slower growing), and whether it arises in myeloid cells or lymphoid cells. Different types of leukemia have a different line of treatment and prognosis.

The physiology of coagulation routes and paths is a cascade of several molecular phenomena and biological events which was classified into two categories based on their phenomena i.e., intrinsic and extrinsic, originated separately, consisting of various factors and features such as fibrinogen, prothrombin, plasma thromboplastin, Hageman factor, Christmas factor, and Stuart-Prower factor, participate in its physiology

Flavopiridol (FVP; alvocidib), an FDA-approved orphan drug, has been studied in clinical trials under both single treatment and combination scenarios; several singleagent Phase I and Phase II clinical trials against leukemia, lymphomas, and solid tumors are active. To date, there have been more than 50 clinical trials involving FVP in the United States. Unfortunately, almost half of patients on FVP clinical trials showed serious adverse effects, implicating appropriate dosages need to be found and an alternative way to circumvent the toxicity of FVP with synergistic agents.

Recent progress in the therapies used for patients with Non- Hodgkin’s lymphoma (NHL) has improved survival. In 2020, 77,240 people were diagnosed with NHL. Although it accounts for 4% of all cancers, the incidence has been reported to be decreasing in the last few years. About 26% of people will expire from NHL (15% males and 11% females).Non-Hodgkin lymphoma arises from the clonal expansion of B, T, and natural killer (NK) cells. There is a significant degree of heterogeneity in NHL and this is likely related to different degrees of differentiation and maturation of these cells. These hematological malignancies exhibit different tumor behavior and are responsive to different chemotherapy agents which impacts clinical outcomes. There are patients who can be cured with current regimens; however, subtypes such as indolent and some aggressive lymphomas remain incurable necessitating treatment with new therapies including immunotherapy, targeted therapy, CAR T cells, and hematopoietic stem cell transplant.

The renewed interest in understanding how activated T cells alter their metabolism to support their growth and differentiation has led to several innovative advances in synthetic biology; culminating in a number of genetic and pharmacologic approaches aimed at improving the antitumor function of adoptively transferred T cells. Indeed, the growing field of immunometabolism has accelerated rapidly giving rise to exciting discoveries and exploratory studies revealing how T cells balance metabolic adaptations in response to intrinsic and extrinsic regulatory cues. Central to this body of work, we showed how chimeric antigen receptors (CAR)-induced metabolic reprogramming is an important determinant of efficacy and clinical outcome in blood-based malignancies.

Platelet preparations (PDPs) have gained success, mainly due to their high concentrations of biologically active molecules, such as growth factors and cytokines, which play an important role in tissue repair and reconstruction. Recent knowledge shows that platelets can play a new role in tissue reproduction and vascular restoration, as well as being the protagonists of inflammatory processes and immune system responses. They release bio-active proteins and other active ingredients that can affect a number of phenomena that promote cell consumption, growth and transformation (growth factors).

Mantle cell lymphoma (MCL) is a rare subtype of non- Hodgkin Lymphoma (NHL) characterized by cyclin D1 translocations. Outcomes are heterogenous, but the disease is generally incurable. High-risk patients been shown to have a median overall survival (OS) of only 37 months and 20% five-year OS. In some patients, the disease is more indolent; such cases are associated with leukemic phase of the disease, SOX11-negativity, and mutated IGHV. Additionally, even across SOX11 positive cases outcomes vary, with worse overall survival in MCL with cytoplasmic staining as compared to nuclear staining. For patients with indolent clinical behavior, observation is frequently employed, and large case series suggest the possibility of prolonged periods before treatment becomes necessary, as long as 128 months, and favorable outcomes even once treatment has been initiated.

Langerhans cell histiocytosis (LCH) is a rare, clonal, haematological disease of myeloid origin involving infiltration of neoplastic cells resembling Langerhans cells in various tissues. LCH cells express normal Langerhans cell markers such as CD1a, Langerin (CD207), and S100.

Multiple myeloma (MM) is a common hematologic malignancy, with 32,110 new cases diagnosed in the United States in 2019, resulting in 12,960 deaths. While neutrophilia
is also a common entity, it most often arises secondary to other etiologies, such as infection or inflammatory processes. 

Recent progress in the therapies used for patients with Non- Hodgkin’s lymphoma (NHL) has improved survival. In 2020, 77,240 people were diagnosed with NHL. Although it accounts for 4% of all cancers, the incidence has been reported to be decreasing in the last few years. About 26% of people will expire from NHL (15% males and 11% females).Non-Hodgkin lymphoma arises from the clonal expansion of B, T, and natural killer (NK) cells. There is a significant degree of heterogeneity in NHL and this is likely related to different degrees of differentiation and maturation of these cells. These hematological malignancies exhibit different tumor behavior and are responsive to different chemotherapy agents which impacts clinical outcomes. There are patients who can be cured with current regimens; however, subtypes such as indolent and some aggressive lymphomas remain incurable necessitating treatment with new therapies including immunotherapy, targeted therapy, CAR T cells, and hematopoietic stem cell transplant.

Gemcitabine is a synthetic pyrimidine nucleoside analogue which is administered intravenously as a chemotherapeutic to treat numerous cancers. Gemcitabine requires transport into cells and activation by phosphorylation, the resulting gemcitabine triphosphate is incorporated into newly synthesized DNA during cell division, inhibiting further DNA synthesis and causing cell death. Gemcitabine is used to treat cancers including those of the pancreas, lung, breast, colon, and ovary either as first or second line treatments as a single agent or in combination.

A 56-year-old Caucasian man was referred to an academic medical center for consideration of allogeneic hematopoietic stem cell transplantation (HSCT). One year earlier, he had seen his primary care physician for increased fatigue and decreased exercise tolerance, and a complete blood cell count showed a total white blood cell count of 2500/μL, hemoglobin of 7.2g/dL, and a platelet count of 110,000/μL. The white blood cell differential showed an absolute neutrophil count of 900/μL. The patient was referred to a hematologist who performed a bone marrow biopsy that showed a myelodysplastic syndrome with del(5q).

Breast cancer is the most frequent malignancy in females. Due to its major impact on the population, this disease represents a critical public health problem that requires further research at the molecular level to define its prognosis and specific treatment. Basic research is required to accomplish this task and this involves cell lines as they can be widely used in many aspects of laboratory research and, particularly, as in vitro models in cancer research. MCF-7 is a commonly used breast cancer cell line, that has been promoted for more than 40 years by multiple research groups but its characteristics have never been gathered in a consistent review article.