scholarly journals Prognosis of Patients with Acute Myeloid Leukemia Regarding the Presence FLT3 Gene Mutation – a Case Report

2017 ◽  
Vol 2 (s4) ◽  
pp. 42-44
Author(s):  
Árpád Bzduch ◽  
István Benedek ◽  
Szilárd Bíró ◽  
Johanna Sándor-Kéri ◽  
Erzsébet Lázár ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Kinase Activity ◽  
Bone Marrow Cells ◽  
Physical Exertion ◽  
Chronic Obstructive ◽  
Tyrosine Kinase Activity ◽  
Pharmacological Agents ◽  
Acute Myeloid

AbstractAcute myeloid leukemia (AML) is a cancerous disease affecting the myeloid line of the bone marrow cells. FLT3, also known as CD135, is a proto-oncogene, which, if mutated, leads to different types of cancer. The protein it encodes presents tyrosine-kinase activity, and its intratandem mutation, FLT3-ITD, leads to uncontrolled proliferation of myeloblasts and worse outcomes in AML patients. There are currently several pharmacological agents that can inhibit the effect of either the proteins with tyrosine-kinase activity or the mutated FLT3 gene. We present the case of a 68-year-old patient, smoker, with a history of arterial hypertension, chronic obstructive pulmonary disease, presenting with headache unresponsive to antalgics, dyspnea after physical exertion, and epistaxis, with onset 2 months prior to his presentation. The patient was diagnosed with AML with positive FTL3 mutation for which conventional induction therapy was initiated. Within the next days, the patient presented several complications related to the disease itself or caused by the treatment, which eventually led to his death.

The cell polarity PTK7 receptor acts as a modulator of the chemotherapeutic response in acute myeloid leukemia and impairs clinical outcome

Blood ◽  
2010 ◽  
Vol 116 (13) ◽  
pp. 2315-2323 ◽  
Author(s):  
Thomas Prebet ◽  
Anne-Catherine Lhoumeau ◽  
Christine Arnoulet ◽  
Anaïs Aulas ◽  
Sylvie Marchetto ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Cell Polarity ◽  
Myeloid Leukemia ◽  
Planar Cell Polarity ◽  
Bone Marrow Cells ◽  
Tyrosine Kinase Receptor ◽  
Epithelial Tissue ◽  
Tissue Organization ◽  
Acute Myeloid

Abstract The pseudo tyrosine kinase receptor 7 (PTK7) is an orphan tyrosine kinase receptor assigned to the planar cell polarity pathway. It plays a major role during embryogenesis and epithelial tissue organization. Here we found that PTK7 is also expressed in normal myeloid progenitors and CD34+ CD38− bone marrow cells in humans. We performed an immunophenotyping screen on more than 300 patients treated for hematologic malignancies. We demonstrated that PTK7 is expressed in acute myeloid leukemia (AML) and is mostly assigned to granulocytic lineage differentiation. Patients with PTK7-positive AML are more resistant to anthracycline-based frontline therapy with a significantly reduced leukemia-free survival in a multivariate analysis model. In vitro, expression of PTK7 in cultured leukemia cells promotes cell migration, cell survival, and resistance to anthracycline-induced apoptosis. The intracellular region of PTK7 is required for these effects. Furthermore, we efficiently sensitized primary AML blasts to anthracycline-mediated cell death using a recombinant soluble PTK7-Fc protein. We conclude that PTK7 is a planar cell polarity component expressed in the myeloid progenitor compartment that conveys promigratory and antiapoptotic signals into the cell and that represents an independent prognosis factor of survival in patients treated with induction chemotherapy.

The Flt3 receptor tyrosine kinase collaborates with NUP98-HOX fusions in acute myeloid leukemia

Blood ◽  
2006 ◽  
Vol 108 (3) ◽  
pp. 1030-1036 ◽  
Author(s):  
Lars Palmqvist ◽  
Bob Argiropoulos ◽  
Nicolas Pineault ◽  
Carolina Abramovich ◽  
Laura M. Sly ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Myeloid Leukemia ◽  
Hox Genes ◽  
Bone Marrow Cells ◽  
Lymphoblastic Leukemia ◽  
Human Leukemia ◽  
Direct Role ◽  
Acute Myeloid

Abstract In leukemogenesis, several genetic changes conferring a proliferative and/or survival advantage to hematopoietic progenitor cells in addition to a block in differentiation are required. Here, we demonstrate that overexpression of the wild-type (wt) Flt3 receptor tyrosine kinase collaborates with NUP98-HOX fusions (NUP98-HOXA10 and NUP98-HOXD13) to induce aggressive acute myeloid leukemia (AML). We used a mouse transplantation model to show their synergism in cotransduced bone marrow cells as well as in a cellular model of leukemic progression. Furthermore, our data support the finding that Meis1 overexpression leads to marked elevation in Flt3 transcription and extend it to the context of NUP98-HOX–induced leukemia. Together, these results support a multistep model where the synergism between NUP98-HOX and wt-Flt3 is the result of the ability of Flt3 to increase proliferation of myeloid progenitors blocked in differentiation by NUP98-HOX fusions and reveal a direct role for wt-Flt3 in the pathobiology of AML. Given the similarities in the leukemogenic role of native HOX and NUP98-fused HOX genes, our results underscore the clinical significance of the recurrent co-overexpression of wt-FLT3 and HOX in human leukemia and suggest that specific FLT3 inhibitors could be useful in treatment of HOX-induced AML or acute lymphoblastic leukemia (ALL).

scholarly journals The P190, P210, and P230 Forms of the BCR/ABL Oncogene Induce a Similar Chronic Myeloid Leukemia–like Syndrome in Mice but Have Different Lymphoid Leukemogenic Activity

1999 ◽  
Vol 189 (9) ◽  
pp. 1399-1412 ◽  
Author(s):  
Shaoguang Li ◽  
Robert L. Ilaria ◽  
Ryan P. Million ◽  
George Q. Daley ◽  
Richard A. Van Etten
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Target Cell ◽  
Myeloid Leukemia ◽  
Kinase Activity ◽  
Philadelphia Chromosome ◽  
Lymphoid Cells ◽  
Tyrosine Kinase Activity ◽  
Lymphoid Leukemia ◽  
B Lymphoid

The product of the Philadelphia chromosome (Ph) translocation, the BCR/ABL oncogene, exists in three principal forms (P190, P210, and P230 BCR/ABL) that are found in distinct forms of Ph-positive leukemia, suggesting the three proteins have different leukemogenic activity. We have directly compared the tyrosine kinase activity, in vitro transformation properties, and in vivo leukemogenic activity of the P190, P210, and P230 forms of BCR/ABL. P230 exhibited lower intrinsic tyrosine kinase activity than P210 and P190. Although all three oncogenes transformed both myeloid (32D cl3) and lymphoid (Ba/F3) interleukin (IL)-3–dependent cell lines to become independent of IL-3 for survival and growth, their ability to stimulate proliferation of Ba/F3 lymphoid cells differed and correlated directly with tyrosine kinase activity. In a murine bone marrow transduction/transplantation model, the three forms of BCR/ABL were equally potent in the induction of a chronic myeloid leukemia (CML)–like myeloproliferative syndrome in recipient mice when 5-fluorouracil (5-FU)–treated donors were used. Analysis of proviral integration showed the CML-like disease to be polyclonal and to involve multiple myeloid and B lymphoid lineages, implicating a primitive multipotential target cell. Secondary transplantation revealed that only certain minor clones gave rise to day 12 spleen colonies and induced disease in secondary recipients, suggesting heterogeneity among the target cell population. In contrast, when marrow from non– 5-FU–treated donors was used, a mixture of CML-like disease, B lymphoid acute leukemia, and macrophage tumors was observed in recipients. P190 BCR/ABL induced lymphoid leukemia with shorter latency than P210 or P230. The lymphoid leukemias and macrophage tumors had provirus integration patterns that were oligo- or monoclonal and limited to the tumor cells, suggesting a lineage-restricted target cell with a requirement for additional events in addition to BCR/ABL transduction for full malignant transformation. These results do not support the hypothesis that P230 BCR/ABL induces a distinct and less aggressive form of CML in humans, and suggest that the rarity of P190 BCR/ABL in human CML may reflect infrequent BCR intron 1 breakpoints during the genesis of the Ph chromosome in stem cells, rather than intrinsic differences in myeloid leukemogenicity between P190 and P210.

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