Acute myeloid leukemia (AML) is a heterogeneous hematopoietic tumor originated from hematopoietic stem cells. FLT3 is an important receptor tyrosine kinase in cell signal transduction pathway and one of the common mutated genes in AML. AML patients with FLT3-ITD mutation have a poor prognosis and tendency to relapse. Therefore, early identification of FLT3 gene mutation and selection of appropriate treatment are particularly important. Currently, the small moleculetargeted drugs have been new treatment methods for AML patients with FLT3-ITD mutation, but accompanied drug resistance need to be solved. This paper reviews the mechanism of FLT3 mutation, the clinical significance of FLT3 mutation in AML, FLT3 inhibitors and drug resistance mechanism.
Humans ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; Signal Transduction ; Receptor Protein-Tyrosine Kinases/therapeutic use* ; Leukemia, Myeloid, Acute/drug therapy* ; fms-Like Tyrosine Kinase 3/genetics*

Animals ; Antibodies, Monoclonal ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; therapeutic use ; Breast Neoplasms ; drug therapy ; Humans ; Receptor Protein-Tyrosine Kinases ; antagonists & inhibitors ; Signal Transduction ; Trastuzumab

Molecule-targeting agents inhibit the proliferation of tumor cells by the molecular biological differences between tumor cells and normal cells, and finally kill tumor cells. This article introduces several molecule-targeting agents that are currently under clinical trials now.
Angiogenesis Inhibitors ; therapeutic use ; Antibodies, Monoclonal ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Erlotinib Hydrochloride ; Humans ; Lung Neoplasms ; drug therapy ; Protein-Tyrosine Kinases ; antagonists & inhibitors ; Quinazolines ; therapeutic use ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors

Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bleomycin ; therapeutic use ; Cyclophosphamide ; therapeutic use ; Dacarbazine ; therapeutic use ; Doxorubicin ; therapeutic use ; Hodgkin Disease ; drug therapy ; Humans ; Lymphoma ; classification ; drug therapy ; pathology ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; Lymphoma, Large-Cell, Anaplastic ; drug therapy ; metabolism ; Lymphoma, Non-Hodgkin ; drug therapy ; Prednisone ; therapeutic use ; Receptor Protein-Tyrosine Kinases ; metabolism ; Rituximab ; Vinblastine ; therapeutic use ; Vincristine ; therapeutic use

The incidence of ALK gene rearrangement in non-small cell lung cancer (NSCLC) was about 3% to 5%. ALK gene inhibitors have made great breakthrough in recent years, significantly extending the survival period of patients with ALK(+) advanced NSCLC. But the majority of patients will be acquired drug resistance after treatment. This article has been explained separately from the ALK genetic background, the detection method, the treatment of the three generations of ALK inhibitors and the strategy after drug resistance. It is desire to have reference value and reference meaning for clinical work.
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Anaplastic Lymphoma Kinase ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; enzymology ; genetics ; Drug Resistance, Neoplasm ; genetics ; Gene Fusion ; Humans ; Lung Neoplasms ; drug therapy ; enzymology ; genetics ; Protein Kinase Inhibitors ; pharmacology ; therapeutic use ; Receptor Protein-Tyrosine Kinases ; antagonists & inhibitors ; genetics

Adult ; Antibodies, Monoclonal ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cyclophosphamide ; therapeutic use ; Diagnosis, Differential ; Doxorubicin ; therapeutic use ; Follow-Up Studies ; Humans ; Leukocyte Common Antigens ; metabolism ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; metabolism ; pathology ; Male ; Mucin-1 ; metabolism ; Prednisone ; therapeutic use ; Receptor Protein-Tyrosine Kinases ; metabolism ; Vincristine ; therapeutic use

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; CD2 Antigens ; metabolism ; Child, Preschool ; Chromosome Breakage ; Cyclophosphamide ; therapeutic use ; Doxorubicin ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Ki-1 Antigen ; metabolism ; Lymphoma, Large-Cell, Anaplastic ; drug therapy ; metabolism ; pathology ; Mucin-1 ; metabolism ; Prednisone ; therapeutic use ; Receptor Protein-Tyrosine Kinases ; genetics ; metabolism ; Vincristine ; therapeutic use

OBJECTIVEThis study aims to evaluate the efficacy and safety of crizotinib for advanced ALK-positive non-small cell lung cancer (NSCLC) patients.

METHODSTwenty-eight patients with advanced ALK-positive NSCLC were given orally crizotinib 250 mg b. i.d., and were followed up to evaluate the therapeutic efficacy and safety.

RESULTSAmong the 28 patients, the objective response rate (ORR) was 71.4% (20/28) and disease control rate (DCR) was 92.9% (26/28). Three patients achieved complete response. Seventeen patients had partial response. The most common drug-related adverse events were mild flickering vision and gastrointestinal reaction. Eleven patients experienced flickering vision. Nine patients had nausea and vomiting. Eight patients had diarrhea. They were all reversible and of grade I or II. Only one patient had grade III myelosuppression. Among the 28 patients, 16 cases were disease-free and 12 cases had progressive disease, with a progression-free survival of 8.2 months.

CONCLUSIONSCrizotinib is effective and tolerable in the treatment of advanced ALK-positive NSLCC. However, its long-term treatment efficacy requires to be further studied.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; enzymology ; pathology ; Diarrhea ; chemically induced ; Disease-Free Survival ; Humans ; Lung Neoplasms ; drug therapy ; enzymology ; pathology ; Nausea ; chemically induced ; Protein Kinase Inhibitors ; adverse effects ; therapeutic use ; Pyrazoles ; adverse effects ; therapeutic use ; Pyridines ; adverse effects ; therapeutic use ; Receptor Protein-Tyrosine Kinases ; Vomiting ; chemically induced

A 31-year-old Korean male presented with altered consciousness and severe headache. Brain MRI delineated focal leptomeningeal enhancement without any intracerebral lesions. Diagnosis was made based on a brain biopsy showing anaplastic large cell lymphoma (ALCL), immunohistochemical stains revealing positivity for anaplastic lymphoma kinase (ALK) and an absence of involvement in any other organs; specifically, the primary central nervous system ALK+ALCL. Complete remission was achieved following 5 cycles of systemic chemotherapy with a high dose of Methotrexate and a simultaneous 7 cycles of intrathecal triple chemotherapy. Diagnosis of primary leptomeningeal ALK+ALCL is challenging given its rarity and non-specific symptoms along with non-pathognomonic radiologic findings. We present the first case of primary leptomeningeal ALK-positive ALCL where the clinical course, pathologic characteristics and treatment modality are described as well as a review of literature.
Adult ; Antineoplastic Agents/therapeutic use ; Biopsy ; Brain/metabolism/pathology ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; Lymphoma, Large-Cell, Anaplastic/*diagnosis/drug therapy/pathology ; Male ; Meningeal Neoplasms/*diagnosis/drug therapy/pathology ; Receptor Protein-Tyrosine Kinases/*metabolism

OBJECTIVE: To evaluate the clinical characteristics, treatment and prognosis of systemic anaplastic large cell lymphoma(sALCL). METHODS: The clinical data of 90 cases with sALCL treated in the Department of Hematology of the Affiliated Xijing Hospital of Air Force Medical University from November 2018 to October 2021 were retrospectively analyzed. The clinical features, treatment and prognosis were summarized and the prognostic factors were investigated. RESULTS: There were 58 males and 32 females, with a median age of 32 (12-73) years old. 69 (76.7%) patients had Ann Arbor stage Ⅲ-Ⅳ disease and half of the patients had extranodal infiltration. The median age was 27(12-72) years of the 60 ALK⁺ patients while 53(15-73) years of the 30 ALK^- patients, and it was significantly different in the age of onset between the two group(P<0.01). 88 patients received first line chemotherapy, and 50(568%) cases achieved complete remission(CR). IPI score≥3 was an independent risk factor for CR. The median progressive free survival(PFS) and overall survival(OS) of the patients were not reached. Multivariate analysis showed that no achievement of CR after first-line therapy was a significant prognostic factor influencing PFS and OS. CONCLUSION sALCL mainly occurs in males and most patients were in advanced stage. Half of the patients had extranodal involvement. The CR rate after first-line chemotherapy was 568%, and IPI score≥3 was a significant prognostic factor for CR. No achievement of CR after first-line therapy is poorly prognostic for PFS and OS.
Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Child ; Disease-Free Survival ; Female ; Humans ; Lymphoma, Large-Cell, Anaplastic/diagnosis* ; Male ; Middle Aged ; Prognosis ; Receptor Protein-Tyrosine Kinases ; Retrospective Studies ; Young Adult