Leukemia, Biphenotypic, Acute
Immunophenotyping
Leukemia
Leukemia, Myeloid, Acute
Novel metabolic pathway of estrone and 17beta-estradiol catalyzed by cytochrome P-450. (1/35)
We have already reported that the quinol formation from some para-alkylphenols, which is a novel metabolic pathway catalyzed by cytochrome P-450, occurs in a rat liver microsomal system (). In the present study, we investigated whether estrone and 17beta-estadiol, each of which contains a p-alkylphenol moiety, are also oxidized into the corresponding quinols by cytochrome P-450. Six recombinant human cytochrome P-450 enzymes, CYP1A1, CYP1A2, CYP2B6, CYP2C9, CYP2E1, and CYP3A4, were tested. The results show that estrone and 17beta-estadiol were converted into the corresponding quinols by CYP1A1, CYP2B6, and CYP2E1. (+info)The polycomb protein MPc3 interacts with AF9, an MLL fusion partner in t(9;11)(p22;q23) acute leukemias. (2/35)
Polycomb group (PcG) proteins assemble to form large multiprotein complexes involved in gene silencing. Evidence suggests that PcG complexes are heterogeneous with respect to both protein composition and specific function. MPc3 is a recently described mouse Polycomb (Pc) protein that shares structural homology with at least two other Pc proteins, M33 and MPc2. All three Pc proteins bind another PcG protein, RING1, through a conserved carboxy-terminal C-box motif. Here, data are presented demonstrating that MPc3 also interacts with AF9, a transcriptional activator implicated in the development of acute leukemias. The carboxy-terminus of AF9 is fused to the MLL protein in leukemias characterized by t(9;11)(p22;q23) chromosomal translocations. Importantly, it is the carboxy-terminus of AF9 to which MPc3 binds. The AF9 binding site of MPc3 maps to a central, non-conserved, region of the polypeptide sequence. In contrast to MPc3, data indicate that the Pc protein M33 does not interact with AF9. This finding suggests a potentially unique role for MPc3 in linking a PcG silencing complex to a transcriptional activator protein. (+info)The RCK gene associated with t(11;14) translocation is distinct from the MLL/ALL-1 gene with t(4;11) and t(11;19) translocations. (3/35)
We previously demonstrated that the 11q23 breakpoint region, designated the RCK locus, of the RC-K8 B-lymphoma cell line with t(11;14)(q23;q32) is centromeric to PBGD, while breakpoints of infantile leukemia cell lines with t(11;19)(q23;p13) are detectable by pulsed-field gel electrophoresis with the CD3D probe. In the present study, using a probe within 1.0 kilobase of the t(11;14) breakpoint, we isolated a partial complementary DNA clone for the putative RCK gene, which detects a 7.5-kilobase mRNA. Sequence analysis predicted a novel protein of 472 amino acids which demonstrated sequence homology to a translation initiation factor/helicase family. We also isolated a phage clone from the CD3D/G yeast artificial chromosome clone (yB22B2) which detects 11- and 12-kilobase mRNAs, most likely for the MLL/ALL-1 gene associated t(4;11)(q21;q23) and t(11;19)(q23;p13) translocations. By pulsed-field gel electrophoresis after NotI digestion, this recombinant clone is on a 96-kilobase fragment, while RCK and PBGD probes are on a more telomeric 690-kilobase NotI fragment. These results, altogether, suggested that two different genes, RCK and MLL/ALL-1, are associated with 11q23 translocation of hematopoietic tumors. (+info)Mixed lineage leukemia translocations and a leukemia stem cell program. (4/35)
Cancer stem cells (CSC) may provide the self-renewal capacity required to sustain a tumor. One possibility is that CSC arise from the stem cell counterparts in normal tissues. Alternatively, CSC may arise from more differentiated progenitor cells found in certain tissues. In support of this idea, we showed recently that mixed lineage leukemia fusion oncoproteins can convert committed hematopoietic progenitors into leukemias, which include leukemia stem cells expressing a self-renewal associated program in the context of a differentiated myeloid cell. The findings suggest a basis to understand the pathobiology of CSC and possible strategies to attack them to undermine the self-renewal capacity of a tumor. (+info)Relationship between in vitro chemosensitivity assessed with MTT assay and clinical outcomes in 103 patients with acute leukemia. (5/35)
BACKGROUND: Cellular drug resistance is supposed to play a major role in chemotherapy failure or relapse. The purpose of this study was to analyze the relationship between in vitro chemosensitivity test results using a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and clinical response on chemotherapy, and to find the possibility of optimizing the treatment protocol for individual patients according to their actual drug resistance. METHODS: For MTT assay, we obtained bone marrow aspirates from 103 patients with acute leukemia at the time of initial diagnosis or relapse. The following drugs were tested: cytarabine, vincristine, methotrexate, daunorubicin, dexamethasone, L-asparaginase, and mitoxantrone. To evaluate clinical responses after induction chemotherapy, we followed up on their bone marrow study. RESULTS: In our study, in vitro chemosensitivity test with the MTT assay significantly predicted whether patients with AML remained continuous complete remission or went into relapse. It also predicted whether or not child patients with ALL would acquire complete remission after induction chemotherapy. CONCLUSIONS: Although it does not provide the insight into the mechanisms that cause drug resistance, the MTT assay may be a useful tool in individually optimizing the chemotherapy of patients with acute leukemia. (+info)Potential use of the Macrobrachium rosenbergii lectin for diagnosis of T-cell acute lymphoblastic leukemia. (6/35)
T-cell acute lymphoblastic leukemia is the most common form of cancer in children. Lectins are proteins or glycoproteins from plants or animals that recognize oligossacharides on the cell surface and have been used to characterize the structural changes of oligosaccharides in leukemias. In this study, we used the lectin from the freshwater prawn Macrobrachium (M. rosenbergii), specific for acetyl groups in sialylated glycans, because increased sialylation of glycoproteins and glycolipids has been identified in lymphoblastic leukemias. We compared the specificity of the M. rosenbergii lectin for lymphoblastic leukemias with the specificities of the lectins from Triticum vulgaris, Solanum tuberosum, Arachis hipogaea, and Phytolacca americana. By morphologic and phenotype characterization with a panel of monoclonal antibodies, we identified four types of leukemias from 106 leukemia patients: 11 cases of T-cell acute lymphoblastic leukemia, 61 cases of B-cell acute lymphoblastic leukemia, 24 cases of acute myeloblastic leukemia, and 10 cases of acute biphenotypic leukemia. As determined by cytofluorometric assays, nine of the eleven cases with T-cell acute lymphoblastic leukemia (8 +/- 3 years old) were specifically identified with the lectin from M. rosenbergii. In contrast, only six cases of B-cell leukemia, one case of myeloblastic leukemia, and 2 cases of biphenotypic leukemia were identified with this M. rosenbergii lectin. The other lectins tested showed no capacity to differentiate, in a significant manner, any of the four types of leukemias tested. Thus, the lectin from M. rosenbergii could be considered a useful tool for the diagnosis and study of T-cell acute lymphoblastic leukemia. (+info)Characterization of childhood acute leukemia with multiple myeloid and lymphoid markers at diagnosis and at relapse. (7/35)
To define the clinical and biologic significance of childhood acute mixed-lineage leukemia diagnosed by stringent criteria, we studied 25 cases of acute lymphoblastic leukemia expressing greater than or equal to 2 myeloid-associated antigens (My+ ALL), and 16 cases of acute myeloid leukemia expressing greater than or equal to 2 lymphoid associated antigens (Ly+ AML). These cases represented 6.1% of 410 newly diagnosed ALLs (two treatment protocols) and 16.8% of 95 AMLs (two protocols). T-lineage--associated antigens were identified in 9 of the My+ ALL cases and in 14 of those classified as Ly+ AML; all but 1 of the 19 cases that could be subclassified had an early thymocyte stage of differentiation. The My+ ALL cases had an increased frequency of French-American-British (FAB) L2 morphology (36%); the Ly+ AML cases were characterized by FAB M1 or M2 morphology, low levels of myeloperoxidase reactivity and combined populations of myeloperoxidase-positive large blasts and small blasts generally of hand-mirror morphology. Karyotypic abnormalities included t(9;22)(q34;q11) in three cases of My+ ALL, 11q23 translocations in two cases of My+ ALL, and 14q32 translocations in three My+ ALL and five Ly+ AML cases. Mixed-lineage expression lacked prognostic significance in either ALL or AML; however, the findings indicate that some patients with Ly+ AML may respond to prednisone, vincristine, and L-asparaginase after failing on protocols for myeloid leukemia. At relapse, two My+ ALLs had converted to AML and two Ly+ AMLs to ALL; one case in each group showed complete replacement of the original karyotype. Acute mixed-lineage leukemia does not adequately describe the heterogeneity of the cases identified in this study and should be replaced by a set of more restrictive terms that indicate the unique biologic features of these leukemias. (+info)Menin, histone h3 methyltransferases, and regulation of cell proliferation: current knowledge and perspective. (8/35)
Menin is a tumor suppressor encoded by the MEN1 gene that is mutated in patients with an inherited syndrome, multiple endocrine neoplasia type 1 (MEN1). Loss of menin has potent impact on proliferation of endocrine and non-endocrine cells. However, until recently little has been known as to how menin regulates cell proliferation. Rapid research progress in the past several years suggests that menin represses proliferation of endocrine cells yet promotes proliferation in certain types of leukemia cells via interacting with various transcriptional regulators. Menin interacts with histone H3 methyltransferases such as MLL (mixed lineage leukemia) protein. Increasing evidence has linked the biological function of menin to epigenetic histone modifications, control of the pattern of gene expression, and regulation of cell proliferation in a cell type-specific manner. In light of these recent findings, an emerging model suggests that menin is a crucial regulator of histone modifiers by acting as a scaffold protein to coordinate gene transcription and cell proliferation in a cell context-dependent manner. This recent progress unravels the coordinating role of menin in epigenetics and regulation of cell cycle, providing novel insights into understanding regulation of beta cell functions and diabetes, as well as the development and therapy of endocrine tumors and leukemia. (+info)Biphenotypic acute leukemia (BAL) is a rare subtype of acute leukemia that possesses the features of both myeloid and lymphoid lineages. It is characterized by the presence of blasts that express antigens associated with both cell lines, which can make it challenging to diagnose and treat. BAL is considered an aggressive form of leukemia and requires prompt medical attention and treatment. The exact cause of BAL is not well understood, but like other forms of leukemia, it is thought to result from genetic mutations that lead to uncontrolled cell growth and division.
Immunophenotyping is a medical laboratory technique used to identify and classify cells, usually in the context of hematologic (blood) disorders and malignancies (cancers), based on their surface or intracellular expression of various proteins and antigens. This technique utilizes specific antibodies tagged with fluorochromes, which bind to the target antigens on the cell surface or within the cells. The labeled cells are then analyzed using flow cytometry, allowing for the detection and quantification of multiple antigenic markers simultaneously.
Immunophenotyping helps in understanding the distribution of different cell types, their subsets, and activation status, which can be crucial in diagnosing various hematological disorders, immunodeficiencies, and distinguishing between different types of leukemias, lymphomas, and other malignancies. Additionally, it can also be used to monitor the progression of diseases, evaluate the effectiveness of treatments, and detect minimal residual disease (MRD) during follow-up care.
Leukemia is a type of cancer that originates from the bone marrow - the soft, inner part of certain bones where new blood cells are made. It is characterized by an abnormal production of white blood cells, known as leukocytes or blasts. These abnormal cells accumulate in the bone marrow and interfere with the production of normal blood cells, leading to a decrease in red blood cells (anemia), platelets (thrombocytopenia), and healthy white blood cells (leukopenia).
There are several types of leukemia, classified based on the specific type of white blood cell affected and the speed at which the disease progresses:
1. Acute Leukemias - These types of leukemia progress rapidly, with symptoms developing over a few weeks or months. They involve the rapid growth and accumulation of immature, nonfunctional white blood cells (blasts) in the bone marrow and peripheral blood. The two main categories are:
- Acute Lymphoblastic Leukemia (ALL) - Originates from lymphoid progenitor cells, primarily affecting children but can also occur in adults.
- Acute Myeloid Leukemia (AML) - Develops from myeloid progenitor cells and is more common in older adults.
2. Chronic Leukemias - These types of leukemia progress slowly, with symptoms developing over a period of months to years. They involve the production of relatively mature, but still abnormal, white blood cells that can accumulate in large numbers in the bone marrow and peripheral blood. The two main categories are:
- Chronic Lymphocytic Leukemia (CLL) - Affects B-lymphocytes and is more common in older adults.
- Chronic Myeloid Leukemia (CML) - Originates from myeloid progenitor cells, characterized by the presence of a specific genetic abnormality called the Philadelphia chromosome. It can occur at any age but is more common in middle-aged and older adults.
Treatment options for leukemia depend on the type, stage, and individual patient factors. Treatments may include chemotherapy, targeted therapy, immunotherapy, stem cell transplantation, or a combination of these approaches.
Acute myeloid leukemia (AML) is a type of cancer that originates in the bone marrow, the soft inner part of certain bones where new blood cells are made. In AML, the immature cells, called blasts, in the bone marrow fail to mature into normal blood cells. Instead, these blasts accumulate and interfere with the production of normal blood cells, leading to a shortage of red blood cells (anemia), platelets (thrombocytopenia), and normal white blood cells (leukopenia).
AML is called "acute" because it can progress quickly and become severe within days or weeks without treatment. It is a type of myeloid leukemia, which means that it affects the myeloid cells in the bone marrow. Myeloid cells are a type of white blood cell that includes monocytes and granulocytes, which help fight infection and defend the body against foreign invaders.
In AML, the blasts can build up in the bone marrow and spread to other parts of the body, including the blood, lymph nodes, liver, spleen, and brain. This can cause a variety of symptoms, such as fatigue, fever, frequent infections, easy bruising or bleeding, and weight loss.
AML is typically treated with a combination of chemotherapy, radiation therapy, and/or stem cell transplantation. The specific treatment plan will depend on several factors, including the patient's age, overall health, and the type and stage of the leukemia.
Precursor Cell Lymphoblastic Leukemia-Lymphoma (previously known as Precursor T-lymphoblastic Leukemia/Lymphoma) is a type of cancer that affects the early stages of T-cell development. It is a subtype of acute lymphoblastic leukemia (ALL), which is characterized by the overproduction of immature white blood cells called lymphoblasts in the bone marrow, blood, and other organs.
In Precursor Cell Lymphoblastic Leukemia-Lymphoma, these abnormal lymphoblasts accumulate primarily in the lymphoid tissues such as the thymus and lymph nodes, leading to the enlargement of these organs. This subtype is more aggressive than other forms of ALL and has a higher risk of spreading to the central nervous system (CNS).
The medical definition of Precursor Cell Lymphoblastic Leukemia-Lymphoma includes:
1. A malignant neoplasm of immature T-cell precursors, also known as lymphoblasts.
2. Characterized by the proliferation and accumulation of these abnormal cells in the bone marrow, blood, and lymphoid tissues such as the thymus and lymph nodes.
3. Often associated with chromosomal abnormalities, genetic mutations, or aberrant gene expression that contribute to its aggressive behavior and poor prognosis.
4. Typically presents with symptoms related to bone marrow failure (anemia, neutropenia, thrombocytopenia), lymphadenopathy (swollen lymph nodes), hepatosplenomegaly (enlarged liver and spleen), and potential CNS involvement.
5. Diagnosed through a combination of clinical evaluation, imaging studies, and laboratory tests, including bone marrow aspiration and biopsy, immunophenotyping, cytogenetic analysis, and molecular genetic testing.
6. Treated with intensive multi-agent chemotherapy regimens, often combined with radiation therapy and/or stem cell transplantation to achieve remission and improve survival outcomes.