The main finding that 18F-FDG PET imaging can reveal in patients with leukemias is the presence of bone marrow (BM) infiltration in both acute or chronic forms. This ability can influence and guide the use of BM biopsy but also assess to therapy response. Additionally 18F-FDG PET imaging has been reported as particularly useful for the diagnosis of leukemias in patients with non specific symptoms. In the case of acute leukemias it revealed also a role for the evaluation of extramedullary forms while in the case of chronic forms a role for the assessment of Richter transformation has been reported.

Leukemia cutis (LC) is defined as the leukemic infiltration of the epidermis, the dermis, and the subcutaneous tissue. Leukemia cutis may follow or occur simultaneously with the diagnosis of systemic leukemia. However, cutaneous lesions are occasionally diagnosed as the primary manifestation of leukemia. Leukemic skin infiltrations demonstrate considerable variation regarding a number of changes, distribution, and morphology. The highest incidence of LC is observed in chronic lymphocytic leukemia, monocytic and myelomonocytic acute myeloid leukemia, and T-cell lineage leukemia. Although the pathogenic mechanism of the invasion of leukemic cells into the skin is not well understood, chemokine receptors and adhesion molecules as well as the genetic characteristics of leukemia are thought to play a role. Leukemic skin lesions may be localized or disseminated and may occur alone or in combination on any site of the skin, most frequently in the trunk and extremities. The most common clinical presentations of leukemia cutis are papules, nodules, macules, plaques, and ulcers. In most patients, the complete or partial resolution of cutaneous infiltrations occurs simultaneously with hematologic remission. However, in patients with resistant disease or recurrent skin infiltration, local radiotherapy can be used. This review presents recent data on the pathogenesis, diagnosis, and treatment of leukemic skin involvement in different types of leukemia.

UNASSIGNED: Leukemic cells express a characteristic set of \"cluster of differentiation\" (CD) markers, which forms the basis of the current WHO classification. Leukemia-associated aberrant immunophenotype (LAIP) refers to expression of unusual CD markers by leukemic cells, which are not normally expressed by their respective lineage. The incidence of LAIP varies considerably, and its clinical implications, prognostic relevance, and sensitivity to therapy are still debatable. This study was conducted to identify the immunophenotypic aberrancies in newly diagnosed leukemias in our Institute.
UNASSIGNED: This was an observational study, which included newly diagnosed leukemias on flow cytometry. Aberrant immunophenotypic expressions were recorded whenever present and were correlated with prognostic factors like age, gender, and total leucocyte count (TLC).
UNASSIGNED: The study included 110 newly diagnosed cases of leukemias (85 acute and 25 chronic) over 1.5 years. Immunophenotypic aberrancies were detected in 40.4% of the cases. The highest incidence of aberrations was detected in acute myeloid leukemia (60.7%). LAIPs were detected in 50% of T-acute lymphoblastic leukemia and 25% cases of in B-cell acute lymphoblastic leukemia (B-ALL). Aberrant CD33 and CD56 expression in B-ALL correlated with poor prognostic factors like higher age and higher TLC, respectively. Immunophenotypic aberrancies were present in 28% cases of chronic lymphocytic leukemia.
UNASSIGNED: The results of this study have generated valuable baseline data on the incidence of LAIPs in this region. This information is vital because establishing LAIPs at the time of diagnosis is crucial for disease monitoring. Some LAIPs are associated with underlying cytogenetic abnormalities and hence impact the management and prognosis.

UNASSIGNED: Chemo-immunotherapies like Fludarabine-Cyclophosphamide-Rituximab (FCR) are used for treatment of chronic lymphocytic leukemia (CLL) in young and fit patients while Bendamustine-Rituximab (BR) is used in older patients. In a resource constrained setting, managing toxicities of FCR chemotherapy is challenging and this study explores the use of upfront BR treatment in young CLL patients (age < 65).
UNASSIGNED: Data of 61 CLL patients treated with the BR regimen between 2016 and 2020 was analysed. Overall-survival and progression-free-survival (OS and PFS) were compared between the two age groups (< / > 65 years) and correlated with the fluorescent-in-situ-hybridization (FISH) data, duration of illness and time to initiation of chemotherapy.
UNASSIGNED: Out of 61 patients, 34 (85%) were below 65 years. Five patients had del 17p and were excluded from the analysis. Forty patients had indications for treatment. Twenty-four (70.5%) of the forty patients achieved overall response; 10 developed progressive disease. The median OS and PFS was 1874 days (95% CI 1617-2130 days) and 1226 days (95% CI 1021-1432 days) respectively and were non inferior between the 2 age-groups. There were no correlations with clinical, laboratory or FISH parameters. The OS and PFS were better for patients with longer time to initiation of chemotherapy as compared to those with short duration of illness and short wait-and-watch periods (p < 0.000).
UNASSIGNED: Our results show that BR chemotherapy can safely and effectively be used in upfront treatment of young CLL patients and provide durable responses.

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in dogs. It is characterized by the proliferation of neoplastic lymphocytes in the bone marrow, which are morphologically normal (mature), but non-functional. CLL in canines commonly originates in cytotoxic T lymphocytes (TCD8+), and although there is controversy regarding the prognostic value of the immunophenotype, this cell lineage may be associated with a good prognosis.
A 10-year-old, entire female, mixed-breed dog was brought to the University Hospital of the Veterinary Faculty (UdelaR) for consultation because a routine pre-surgical check-up revealed lymphocytic leukocytosis, normocytic anemia, and hyperglobulinemia due to an oligoclonal gammopathy. The ultrasound revealed splenomegaly. PCR performed on blood was negative for Ehrlichia canis. Blood and bone marrow flow cytometry was performed to complement the diagnosis and carry out the immunophenotype, which showed CLL of CD8+ T-cell lineage. The clinical suspicion of CLL was confirmed by a myelogram. Chemotherapy treatment based on alkylating agents and glucocorticoids was established. So far, the patient has an overall survival of 13 months with a good response to treatment.
The combination of the immunophenotyping test, the myelogram, and the hematological and biochemical profile confirmed the presence of T-CLL in our patient. Flow cytometry, increasingly used in veterinary medicine, allowed us to confirm the diagnosis of CLL originating in cytotoxic T lymphocytes in our patient, through the presence of positive staining of primary antibodies specific for the canine species CD45, CD3, CD5, and CD8 and the absence of staining for CD4, CD21, and CD34.

Until now, morphological assessment with an optical or electronic microscope, fluorescence in situ hybridization, DNA sequencing, flow cytometry, polymerase chain reactions, and immunohistochemistry have been employed for leukemia identification. Nevertheless, despite their numerous different vantages, it is difficult to recognize leukemic cells correctly. Recently, the electrochemical evaluation with a nano-sensing interface seems an attractive alternative. Electrochemical biosensors measure the modification in the electrical characteristics of the nano-sensing interface, which is modified by the contact between a biological recognition element and the analyte objective. The implementation of nanosensors is founded not on single nanomaterials but rather on compilating these components efficiently. Biosensors able to identify the molecules of deoxyribonucleic acid are defined as DNA biosensors. Our review aimed to evaluate the literature on the possible use of electrochemical biosensors for identifying hematological neoplasms such as acute promyelocytic leukemia, acute lymphoblastic leukemia, and chronic myeloid leukemia. In particular, we focus our attention on using DNA electrochemical biosensors to evaluate leukemias.

Acute lymphoblastic leukemia (ALL) is hematological neoplasia that affects human beings from early life to adulthood. Although ALL treatment has been effective, an important percentage of ALL patients are resilient to treatment. Therefore, there is an urgent need for testing a new combination of compounds for the treatment of this disease. Recently, combined TPEN and TPGS (T2 combo) have shown selective cytotoxic effects in vitro leukemia cells such as Jurkat, K562, and Ba/F3 cells. In this study, we aimed to test the effect of combined TPEN and TPGS agents (T2 combo) at a fixed dose (TPEN 5 mg/kg: TPGS 100 mg/kg) on leukemic Ba/F3-BCR-ABL P210 BALB-c mice model. We found that 4 successive 2-day apart intravenous injections of T2 combo showed a statistically significant reduction of Ba/F3 BCR-ABL leukemia cells (- 69%) in leukemia BALB/c mice (n = 6) compared to untreated leukemia group (n = 6). Moreover, the T2 combo was innocuous to non-leukemia BALB/c mice (n = 3) compared to untreated non-leukemia mice (control, n = 3). After treatments (day 42), all mice were left to rest until day 50. Outstandingly, the leukemia BALB/c mice treated with the T2 combo showed a lower percentage of Ba/F3-BCR-ABL P210 cells (- 84%) than untreated leukemia BALB/c mice. Furthermore, treatment of leukemia and non-leukemia mice with T2 combo showed no significant tissue alteration/damage according to the histopathological analysis of brain, heart, liver, kidney, and spleen samples; however, T2 combo significantly reduced the number of leukocytes in the bone marrow of treated leukemia mice. We conclude that the T2 combo specifically affects leukemia cells but no other tissue/organs. Therefore, we anticipate that the T2 combo might be a potential pro-oxidant combination for the treatment of leukemia patients.

TPEN and TPGS have recently shown selective cytotoxic effects in vitro and ex vivo leukemia cells. In this study, we aimed to test the synergistic effect of combined TPEN and TPGS agents (thereafter, T2 combo) on Jurkat (clone-E61), K562, Ba/F3, and non-leukemia peripheral blood lymphocytes (PBL). The ED50 doses (i.e., TPEN ED50: 3.2 μM and TPGS ED50: 34 μM, potency ratio R = 10.62 = TPGS (ED50)/TPEN (ED50)) were identified as dose-effect curve (%DNA fragmentation (sub-G1 phase) versus agent concentration). The most effective synergistic doses were determined according to isobole analysis. The apoptotic and oxidative stress effects of combined doses (TPEN 0.1, 0.5, 1 μM) and TPGS (5, 10, 20 μM)) were evaluated by DNA fragmentation (sub-G1 phase), mitochondrial membrane potential, oxidation of stress sensor protein DJ-1, and activation of executer protein CASPASE-3. They testified to the synergistic effect of the T2 combo (e.g., TPEN 1: TPGS 20, combination index (CI) 0.90 < 1; 1/3.2+ 20/34, > 90% induced apoptosis) in all 3 cell lines. As proof of principle, we challenged complete bone marrow (n = 5) or isolated cells from bone marrow (n = 3) samples from acute pediatric acute B-cell patients and found that T2 combo (1:20; 10:200) dramatically reduced (- 50%) the CD34+/CD19+cell population and increased significantly CD19+/CASP-3+ positive B-ALL cells up to 960%. The T2 combo neither induced DNA fragmentation, altered ΔΨm, nor induced oxidation of stress sensor protein DJ-1, nor activated CASP-3 in PBL cells. We conclude that by using different combinations of TPEN and TPGS, a more efficient treatment strategy can be developed for leukemia patients.

Leukemia is a lethal cancer in which white blood cells undergo proliferation and immature white blood cells are seen in the bloodstream. Without diagnosis and management in early stages, this type of cancer can be fatal. Changes in protooncogenic genes and microRNA genes are the most important factors involved in development of leukemia. At present, leukemia risk factors are not accurately identified, but some studies have pointed out factors that predispose to leukemia. Studies show that in the absence of genetic risk factors, leukemia can be prevented by reducing the exposure to risk factors of leukemia, including smoking, exposure to benzene compounds and high-dose radioactive or ionizing radiation. One of the most important treatments for leukemia is chemotherapy which has devastating side effects. Chemotherapy and medications used during treatment do not have a specific effect and destroy healthy cells besides leukemia cells. Despite the suppressing effect of chemotherapy against leukemia, patients undergoing chemotherapy have poor quality of life. So today, researchers are focusing on finding more safe and effective natural compounds and treatments for cancer, especially leukemia. Chitosan is a valuable natural compound that is biocompatible and non-toxic to healthy cells. Anticancer, antibacterial, antifungal and antioxidant effects are examples of chitosan biopolymer properties. The US Food and Drug Administration has approved the use of this compound in medical treatments and the pharmaceutical industry. In this article, we take a look at the latest advances in the use of chitosan in the treatment and improvement of leukemia.

αvβ3 integrin, a plasma membrane protein, is amply expressed on an array of tumors. We identified nuclear αvβ3 pool in ovarian cancer cells and were interested to explore this phenomenon in two rare and aggressive types of leukemia, T-cell acute lymphoblastic leukemia (T-ALL) and Mast cell leukemia (MCL) using Jurkat and HMC-1 cell lines, respectively. Moreover, we collected primary cells from patients with chronic lymphocytic leukemia (CLL, n = 11), the most common chronic adult leukemia and used human lymphoblastoid cell lines (LCL) generated from normal B cells. Nuclear αvβ3 integrin was assessed by Western blots, confocal microscopy, and the ImageStream technology which combines flow-cytometry with microscopy. We further examined post translational modifications (phosphorylation/glycosylation), nuclear trafficking regulation using inhibitors for MAPK (U0126) and PI3K (LY294002), as well as nuclear interactions by performing Co-immunoprecipitation (Co-IP). αvβ3 integrin was identified in all cell models within the nucleus and is N-glycosylated. In primary CLL cells the β3 integrin monomer is tyrosine Y759 phosphorylated, suggesting an active receptor conformation. MAPK and PI3K inhibition in Jurkat and CLL cells led to αvβ3 enhancement in the nucleus and a reduction in the membrane. The nuclear αvβ3 integrin interacts with ERK, Histone H3 and Lamin B1 in Jurkat, Histone H3 in CLL cells, but not in control LCL cells. To conclude, this observational study provides the identification of nuclear αvβ3 in hematological malignancies and lays the basis for novel cancer-relevant actions, which may be independent from the membrane functions.