Acute pancreatitis as initial presentation of acute myeloid leukemia-M2 subtype:A case report

BACKGROUND Direct infiltration of the pancreas by acute myeloid leukemia(AML)with acute pancreatitis(AP)as an initial symptom is extremely rare.Only once in the literature,the leukemia cells in AML have been implicated as the cause of AP.Pancreatitis caused by a rare predisposing factor is often misdiagnosed as idiopathic pancreatitis or pancreatitis of other common causes.Severe AP(SAP)progresses rapidly with a high fatality rate.Therefore,it is important to identify the predisposing factors in the early stage of SAP,evaluate the condition,determine prognosis,formulate treatment plans,and prevent a recurrence.Here,we describe a case of SAP due to AML.CASE SUMMARY A 61-year-old man presented to the hospital with fever and persistent abdominal pain.Blood analysis presented significantly elevated serum amylase and severe thrombocytopenia.Computed tomography examination of the abdomen revealed peripancreatic inflammatory effusion.The patient had no common etiologies and risk factors for AP,but the concurrent severe thrombocytopenia could not be explained by pancreatitis.Finally,the bone marrow aspirate and biopsy inspection revealed the underlying reason for pancreatitis,AML(M2 type based on the French-American-British classifications system).CONCLUSION Direct infiltration of the pancrease by acute leukemia,particularly AML cells,is an infrequent cause of AP.Therefore,although AP is a rare extramedullary infilt-ration characteristic for AML patients,it should be considered when determining the etiology of AP.

Up-regulation of TIMP-2 expression promotes SHI-1 leukemic cells proliferation and infiltration in immunodeficiency mice

Background MMPs and TIMPs play important roles in tumor angiogenesis and invasion. Studies have shown that TIMP- 2 has two roles in tumor invasion. However, its role in leukemic infiltration has not been well investigated. This study explored the roles of TIMP-2 in extramedullary infiltration of acute monocytic leukemic SHI-1 cells both in vitro and in vitro. Methods A retroviral vector carrying the human TIMP-2 cDNA was constructed and transfected into the monocytic leukemic cell line SHI-I. The expression of TIMP-2 in the positive clones was determined. The proliferation of SHI-1 cells was examined by MTT assay. Trans-Matrigel invasion assays were used to investigate the infiltration ability in vitro. SHI-1 cells were intravenously injected into pre-traated nu/nu mice to investigate the infiltration ability feature in vitro. Results The expression of TIMP-2 on the cell membrane was significantly elevated in SHI-1/TIMP-2 cells. Over- expression of TIMP-2 promoted the cells proliferation and the invasions in vitro. The SHI-1/TIMP-2 cells demonstrated higher infiltration ability when intravenously injected into nu/nu mice. Conclusion Over-expression of TIMP-2, especially on the cell membrane, may play important roles in promoting the proliferation and infiltration of SHI-1 leukemic cells.

Molecular and cellular aspects of extramedullary manifestations of acute myeloid leukemia

The myeloid extramedullary tumor is a solid tumor formed by infiltration of immature myeloid cells in various tissues of the body.This tumor is also identified as chloroma or myeloid sarcoma(MS).MS is a manifestation of acute myeloid leukemia(AML)occurring at presentation or during treatment or relapse.MS is associated with multiple chromosomal abnormalities and molecular mutations since patients with these disorders bear a high potential for MS manifestation.There is a high incidence of extramedullary infiltration(EMI)in AML.AML patients with EMI have a worse prognosis than patients without it.Hematopoietic stem cells and leukemic stem cells reside in a special bone marrow microenvironment called niche,which is essential for their normal functions.Cancers are exploited dysfunctional cell-cell and matrix-cell interactions,which convert a normal niche into a neoplastic niche.This study summarizes the current knowledge on the molecular and cellular characteristics of AML with EMI and extramedullary niches in AML patients.

Direct contact with bone marrow stromal cells promotes the invasions of SHI-1 leukemia cells

Background Interactions of tumor cells with the microenvironment were deemed to promote the tumor invasion and metastasis. CXC chemokine receptor 4 （CXCR4） and extracellular matrix metalloproteinase inducer （EMMPRIN） had reported to participate in this process. However the roles of bone marrow microenvironment in leukemic infiltration were not well investigated. Methods A co-culture system between SHI-1 cells and bone marrow stromal cells （BMSCs） is used to simulate the interactions of leukemic cells with their microenvironment. The trans-matrigel invasion was used to detect the capability of SHI-1 cells invasion. The BMSCs and SHI-1 cells were mixed in a ratio of 1：10 and added to the millicell chamber coated with matrigel. Either the co-culture supernatant or the functional blocking peptide of CXCR4 and EMMPRIN were added to the trans-matrigel invasion system. The expressions of EMMPRIN in SHI-1 cells and BMSCs were detected by RT-PCR. The changes of the expression of matrix metalloproteinase-2, 9 （MMP-2, MMP-9）, tissue inhibitor of metalloproteinase 2 （TIMP-2）, and CXCR4 mRNA in SHI-1 cells were determined by real-time PCR. The concentration of stromal cell derived factor 1 （SDF-1） in serum free supernatant was measured by ELISA. Results Both SHI-1 cells and BMSCs express EMMPRIN. SHI-1 cells could hardly invade the matrigel membrane; the co- culture supernatant did not induce the invasion of SHI-1 cells. When contacting directly with BMSCs, SHI-1 cells invaded to the lower chamber of millicell were significantly increased. The functional blocking peptide of CXCR4 and EMMPRIN could significantly inhibit the invasion triggered by BMSCs. When co-culturing with BMSCs, the expression of CXCR4, MMP-2, MMP-9 and TIMP-2 mRNA in SHI-1 cells were significantly elevated in company with a significantly higher level of SDF-1 in the co-cultured serum-free supernatant. Conclusion The interactions of leukemic cells and BMSCs play important roles in leukemic cell infiltration.