Nucleophosmin protein (npm) mutants, corresponding gene sequences and uses thereof

A protein and sequence technology, applied in the field of acute myeloid leukemia markers, can solve problems such as unreasonable morphological standards

Inactive Publication Date: 2008-04-09
B·法利尼 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, they cannot be considered normal karyotype-specific as they are also present in LAM cases with more chromosomal translocations (Carnicer et al., 2004) and in acute secondary myeloid leukemia (Christiansen et al. , 2001)
[0009] Thus, to date, no diagnostic / predictive test or molecular marker exists that specifically detects and differentiates primary normal karyotypic LAMs whose characterization and classification is still based on unreasonable morphological criteria

Method used

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  • Nucleophosmin protein (npm) mutants, corresponding gene sequences and uses thereof
  • Nucleophosmin protein (npm) mutants, corresponding gene sequences and uses thereof
  • Nucleophosmin protein (npm) mutants, corresponding gene sequences and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0183] Example 1 : Gene expression of NPM and its diagnostic and predictive value in LAMs

[0184] Studies have been performed to identify a large subpopulation of acute myeloid leukemia (approximately one-third of LAMs in adults) characterized by the localization of cytoplasmic NPM in leukaemic blasts to the NPM gene Mutations, high frequency of normal karyotype, and rapid response to induction chemotherapy.

[0185] Materials and methods

[0186] Tumor samples and patients

[0187] Immunohistochemical studies have been performed on 1845 paraffin-embedded tumor samples. LAMs included: 591 primary LAMs (age 15-60, excluding M3 subgroup) and 70 acute promyelocytic leukemias from the GIMEMA / EORTC study AML12, 69 primary and 135 secondary Out-of-protocol LAMs (69 primary and 135 secondary LAMs out protocol). The remaining samples indicated hematopoietic and extra-haemopoietic tumors, but not LAM.

[0188] After notification of approval, osteomedullary biopsies from each pa...

Embodiment 2

[0243] Example 2: Generation of specific antibodies against the polypeptide sequence of leukemia-specific NPM C-terminus

[0244] Polypeptide sequences represent ideal immune genes for the production of specific antibodies, including various types of polyclonal and monoclonal antibodies, human monoclonal antibodies, and humanized antibodies produced by genetic recombination methods.

[0245] and Figure 4 Peptides corresponding to the sequences A, B, C, D, E and F in B can be chemically synthesized according to standard methods.

[0246] Every animal species can be used for antibody production. The methods used for antibody production and the immunization methods of the animal species (route of vaccination of the antigen, use of Freund's adjuvant to increase the immunogenicity of the injected mixture, frequency of immunization, etc.) are well described in the scientific literature.

[0247] monoclonal

[0248] Balb / c mice can be vaccinated intraperitoneally with a specifi...

Embodiment 3

[0269] Example 3 : Preparation of vaccines

[0270] Vaccines may be administered in formulations recognized by "T cell receptors" (monocytes from peripheral blood) or present with antigen-presenting cells (eg, dendritic cells, B cells, macrophages).

[0271] In this context, the term "vaccine" refers to any substance or compound that acts to induce anti-tumor immunity, which refers to the cytotoxic response (of T cells), and induces antibodies that recognize tumor cells and produce cytokines. Antitumor activity can be determined in vitro (cytotoxicity) or in vivo in experimental animal models.

[0272] It is known that the effect of anti-tumor vaccines increases when used in combination with various polypeptides having different structures. Therefore, for this purpose, anti-LAM NPMc+ vaccines can contain various synthetic polypeptides with different specificities and sequences and allow them to induce recognition of tumor cells containing mutations in the NPM gene.

[027...

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Abstract

The invention relates to new nucleophosmin protein (NPM) mutants, corresponding gene sequences and relative uses thereof for diagnosis, monitoring of minimal residual disease; prognostic evaluation and therapy of the acute myeloid leukaemia (AML).

Description

technical field [0001] The present invention relates to a new nucleophosmin mutant, its corresponding gene sequence and its diagnostic application for monitoring minor sequelae, predicting evaluation and treating acute myelogenous leukemia (LAM). [0002] More specifically, the present invention relates to novel cytoplasmic nucleophosmin (NPM) mutants and their corresponding gene sequences and their use as markers for diagnosis, prediction and treatment of acute myeloid leukemia with normal karyotype. Background technique [0003] Primary acute myeloid leukemia, the most common form of leukemia in adults, is a disease that starts in the bone marrow, more commonly from pluripotent or multipotentl stem cells that have committed to myelopoiesis. Tumorogenic transformation improves the mechanisms that regulate stem cell proliferation and differentiation by preventing the maturation of stem cell progeny. The consequences of this event are cumulative, primarily in the bone marrow...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/47C07K16/30
CPCC07K14/47C12Q1/6886C12Q2600/156C12Q2600/158C12Q2600/106G01N33/57426G01N2333/4704
Inventor B·法利尼C·梅库奇
Owner B·法利尼
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