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Epstein-Barr virus-negative aggressive natural killer-cell leukaemia with high P-glycoprotein activity and phosphorylated extracellular signal-regulated protein kinases 1 and 2.

Perkovic S, Basic-Kinda S, Gasparovic V, Krznaric Z, Babel J, Ilic I, Aurer I, Batinic D - Hematol Rep (2012)

Bottom Line: The patient was treated with an intensive polychemotherapy regimen designed for treatment of acute lymphoblastic leukaemia, but one month after admission developed sepsis, coma and died of cardiorespiratory arrest.We present additional evidence that, except for the immunophenotype, leukaemic NK-cells resemble normal NK-cells in terms of P-gp functional capacity and expression of phosphorylated ERK1/2 signalling molecule.In that sense drugs that block P-glycoprotein activity and activated signalling pathways might represent new means for targeted therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Diagnostics, Division of Immunology and Department of Internal Medicine;

ABSTRACT
Aggressive natural killer-cell leukaemia (ANKL) is a rare type of disease with fulminant course and poor outcome. The disease is more prevalent among Asians than in other ethnic groups and shows strong association with Epstein-Barr virus (EBV) and P-glycoprotein (P-gp) expression associated with multidrug resistance. Here we present a case of a 47 year old Caucasian female with a prior medical history of azathioprine treated ulcerative colitis who developed EBV-negative form of ANKL. The patient presented with hepatosplenomegaly, fever and nausea with peripheral blood and bone marrow infiltration with up to 70% of atypical lymphoid cells positive for cCD3, CD2, CD7, CD56, CD38, CD45, TIA1 and granzyme B, and negative for sCD3, CD4, CD5, CD8, CD34 and CD123 indicative of ANKL. Neoplastic CD56(+) NK-cells showed high level of P-glycoprotein expression and activity, but also strong expression of phosphorylated extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) MAP kinase. The patient was treated with an intensive polychemotherapy regimen designed for treatment of acute lymphoblastic leukaemia, but one month after admission developed sepsis, coma and died of cardiorespiratory arrest. We present additional evidence that, except for the immunophenotype, leukaemic NK-cells resemble normal NK-cells in terms of P-gp functional capacity and expression of phosphorylated ERK1/2 signalling molecule. In that sense drugs that block P-glycoprotein activity and activated signalling pathways might represent new means for targeted therapy.

No MeSH data available.


Related in: MedlinePlus

Bone marrow aspirate (A). The blasts have large nuclei with fine chromatin, a single nucleolus, and a moderate amount of light blue cytoplasm (May-Grünwald Giemsa stain, 1000×). Bone marrow biopsy (B, C). Immunohistochemically, tumor cells are CD56+ (B) and show granular cytoplasmic reaction when stained for TIA1 (C) (40×).
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Figure 1: Bone marrow aspirate (A). The blasts have large nuclei with fine chromatin, a single nucleolus, and a moderate amount of light blue cytoplasm (May-Grünwald Giemsa stain, 1000×). Bone marrow biopsy (B, C). Immunohistochemically, tumor cells are CD56+ (B) and show granular cytoplasmic reaction when stained for TIA1 (C) (40×).

Mentions: Peripheral blood and bone marrow smears revealed up to 70% of atypical lymphoid cells. The morphology (medium/large granular cells, round nucleus, intermediate condensed chromatin, pronounced nucleolus and basophilic cytoplasm) (Figure 1A) and cytochemical pattern (MPO−, SUDAN−, ANAE-, PAS+/−) of these cells was indicative of lymphoproliferative disease. Bone marrow biopsy revealed reduction of all three haematopoietic cell lineages and diffuse interstitial infiltrate of medium sized to large atypical lymphoid cells. Immunohistochemically, the cells were CD56+, TIA1+ (Figures 1B and C), granzyme B+, cytoplasmic CD3+, CD4− and CD20−. Flow cytometry of bone marrow aspirate revealed relatively homogenous population of cells (65%) positive for CD45, cCD3, CD2, CD7, CD38, CD56, and negative for sCD3, CD4, CD5, CD8, CD13, CD117, CD34, HLA-DR, TdT and CD123. Karyotyping showed no chromosome abnormalities (46, XX). Considering all of the above, the patient was diagnosed with aggressive NK-cell leukaemia.


Epstein-Barr virus-negative aggressive natural killer-cell leukaemia with high P-glycoprotein activity and phosphorylated extracellular signal-regulated protein kinases 1 and 2.

Perkovic S, Basic-Kinda S, Gasparovic V, Krznaric Z, Babel J, Ilic I, Aurer I, Batinic D - Hematol Rep (2012)

Bone marrow aspirate (A). The blasts have large nuclei with fine chromatin, a single nucleolus, and a moderate amount of light blue cytoplasm (May-Grünwald Giemsa stain, 1000×). Bone marrow biopsy (B, C). Immunohistochemically, tumor cells are CD56+ (B) and show granular cytoplasmic reaction when stained for TIA1 (C) (40×).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3475938&req=5

Figure 1: Bone marrow aspirate (A). The blasts have large nuclei with fine chromatin, a single nucleolus, and a moderate amount of light blue cytoplasm (May-Grünwald Giemsa stain, 1000×). Bone marrow biopsy (B, C). Immunohistochemically, tumor cells are CD56+ (B) and show granular cytoplasmic reaction when stained for TIA1 (C) (40×).
Mentions: Peripheral blood and bone marrow smears revealed up to 70% of atypical lymphoid cells. The morphology (medium/large granular cells, round nucleus, intermediate condensed chromatin, pronounced nucleolus and basophilic cytoplasm) (Figure 1A) and cytochemical pattern (MPO−, SUDAN−, ANAE-, PAS+/−) of these cells was indicative of lymphoproliferative disease. Bone marrow biopsy revealed reduction of all three haematopoietic cell lineages and diffuse interstitial infiltrate of medium sized to large atypical lymphoid cells. Immunohistochemically, the cells were CD56+, TIA1+ (Figures 1B and C), granzyme B+, cytoplasmic CD3+, CD4− and CD20−. Flow cytometry of bone marrow aspirate revealed relatively homogenous population of cells (65%) positive for CD45, cCD3, CD2, CD7, CD38, CD56, and negative for sCD3, CD4, CD5, CD8, CD13, CD117, CD34, HLA-DR, TdT and CD123. Karyotyping showed no chromosome abnormalities (46, XX). Considering all of the above, the patient was diagnosed with aggressive NK-cell leukaemia.

Bottom Line: The patient was treated with an intensive polychemotherapy regimen designed for treatment of acute lymphoblastic leukaemia, but one month after admission developed sepsis, coma and died of cardiorespiratory arrest.We present additional evidence that, except for the immunophenotype, leukaemic NK-cells resemble normal NK-cells in terms of P-gp functional capacity and expression of phosphorylated ERK1/2 signalling molecule.In that sense drugs that block P-glycoprotein activity and activated signalling pathways might represent new means for targeted therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Diagnostics, Division of Immunology and Department of Internal Medicine;

ABSTRACT
Aggressive natural killer-cell leukaemia (ANKL) is a rare type of disease with fulminant course and poor outcome. The disease is more prevalent among Asians than in other ethnic groups and shows strong association with Epstein-Barr virus (EBV) and P-glycoprotein (P-gp) expression associated with multidrug resistance. Here we present a case of a 47 year old Caucasian female with a prior medical history of azathioprine treated ulcerative colitis who developed EBV-negative form of ANKL. The patient presented with hepatosplenomegaly, fever and nausea with peripheral blood and bone marrow infiltration with up to 70% of atypical lymphoid cells positive for cCD3, CD2, CD7, CD56, CD38, CD45, TIA1 and granzyme B, and negative for sCD3, CD4, CD5, CD8, CD34 and CD123 indicative of ANKL. Neoplastic CD56(+) NK-cells showed high level of P-glycoprotein expression and activity, but also strong expression of phosphorylated extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) MAP kinase. The patient was treated with an intensive polychemotherapy regimen designed for treatment of acute lymphoblastic leukaemia, but one month after admission developed sepsis, coma and died of cardiorespiratory arrest. We present additional evidence that, except for the immunophenotype, leukaemic NK-cells resemble normal NK-cells in terms of P-gp functional capacity and expression of phosphorylated ERK1/2 signalling molecule. In that sense drugs that block P-glycoprotein activity and activated signalling pathways might represent new means for targeted therapy.

No MeSH data available.


Related in: MedlinePlus