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Significance of GRP78 expression in acute myeloid leukemias

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Wróbel T., Stefanko E., Dzietczenia J., Jaźwiec B., Mazur G., Haus O., Dybko J., Kuliczkowski K.

Open Medicine

2014

vol. 9

issue 2

204-209

The GRP78 (glucose-regulated protein 78) is a major endoplasmic reticulum (ER) chaperone facilitating proper folding of the newly synthesized proteins. By the interaction with caspases, GRP78 has antiapoptotic properties allowing cells to survive under stress condition. GRP78 expression and its association with tumor proliferation, metastasis and resistance to chemotherapy were observed in solid tumors. There are limited data on the expression and impact of this protein on the clinical course and treatment response in acute myeloid leukemia (AML). The aim of this study was to evaluate the expression of GRP78 mRNA in patients with de novo AML. These results were compared to healthy controls, blast phenotype, molecular and cytogenetic status and clinical features of AML. 101 non-M3 AML patients and 26 healthy individuals were included in this study. The expression of GRP78 mRNA in bone marrow was analyzed by real-time quantitative polymerase chain reaction (RQ-PCR). We demonstrated increased GRP78 mRNA expression in AML patients compared to healthy controls, although this difference was statistically significant only in CD34+ leukemias. There was also no significant correlation between GRP78 mRNA expression and complete remission rate, relapse-free survival and overall survival. These results indicate that GRP78 expression is increased in CD34+ leukemias and has no prognostic impact on clinical outcome in AML.

The effect of lipegfilgrastim on hematopoietic reconstitution and supportive treatment after megachemotherapy with autologous peripheral blood stem cell transplantation in patients with lymphoproliferative malignancies

100%

Frączak E., Dybko J., Rybka J., Biedroń M., Dereń-Wagemann I., Urbaniak-Kujda D., Kuliczkowski K., Wróbel T.

OncoReview

2016

vol. 6

issue 2

A66-71

Megachemotherapy with autologous peripheral blood stem cell transplantation (auto-PBSCT) is a standard treatment option in patients below 70 years of age with multiple myeloma (MM) as well as with relapsed and refractory lymphomas. Recombinant granulocyte colony-stimulating factors (G-CSF) are commonly used to accelerate bone marrow recovery after chemotherapy and reduce the duration of severe neutropenia. Lipegfilgrastim is a glicopegylated G-CSF with prolonged action registered for adult patients with malignant neoplasms in order to reduce the duration of neutropenia and the incidence of febrile neutropenia (FN). So far, there is not enough data to confirm the effectiveness and safety of this drug in patients with hematological malignancies including those undergoing auto-PBSCT. The aim of this study was to determine the effect of lipegfilgrastim on hematopoietic regeneration and supportive care after auto-PBSCT in patients with lymphoproliferative malignancies. The study population consisted of 30 patients (12 female and 18 male; median age: 50 years ± 13), including 13 patients with MM, 5 with Hodgkin’s lymphoma (HL) and 12 with non-Hodgkin’s lymphoma (nHL). The median number of transplanted CD34+ cells was 3.96 ± 1.56 × 10^6/kg of body mass. On day +1 after auto-PBSCT, the patients received lipegfilgrastim in a single 6 mg subcutaneous injection. The control group consisted of 32 patients (13 female and 19 male; median age: 50 years ± 6.4), including 13 with MM, 8 with HL and 11 with nHL, who received subcutaneous filgrastim in a dose of 5 μg/kg/day from day +1 after transplantation and continued to an absolute neutrophil count (ANC) > 1.5 × 10^9/L. There was no significant difference in the time of regeneration ANC > 0.5 × 10^9/L which was 10.65 ± 1.00 vs. 11.51 ± 2.29 days respectively in the study and control group. Similar observations were noted regarding the duration of febrile neutropenia (2.16 ± 2.22 vs. 1.70 ± 4.17 days; p = 0.998), regeneration of platelets (PLT) > 20 × 10^9/L (12.41 ± 2.41 vs. 13.82 ± 4.48 days; p = 0.233) and demand for transfusion of red blood cells (0.76 ± 1.07 vs. 1.33 ± 2.33 units; p = 0.414) and platelets (11.5 ± 6.9 vs. 19.2 ± 17.7 units; p = 0.08). Different results were observed for the length of hospitalization, which was significantly shorter in the lipegfilgrastim group (16.14 ± 14 vs. 24.46 ± 6.79 days; p = 0.000). Lipegfilgrastim is as effective as filgrastim with regards to the regeneration of the hematopoietic system, duration of febrile neutropenia, demand for transfusion of blood products and significantly reduces hospitalization in patients with lymphoproliferative malignancies after auto-PBSCT.

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1 OncoReview

1 Open Medicine

1 2016

1 2014

2 Dybko J.

2 Kuliczkowski K.

2 Wróbel T.

1 Biedroń M.

1 Dereń-Wagemann I.

1 Dzietczenia J.

1 Frączak E.

1 Haus O.

1 Jaźwiec B.

1 Mazur G.

1 Rybka J.

1 Stefanko E.

1 Urbaniak-Kujda D.

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Significance of GRP78 expression in acute myeloid leukemias

The effect of lipegfilgrastim on hematopoietic reconstitution and supportive treatment after megachemotherapy with autologous peripheral blood stem cell transplantation in patients with lymphoproliferative malignancies