Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1
5-Year Impact Factor – 2.2
Scopus CiteScore – 3.4 (CiteScore Tracker 3.7)
Index Copernicus  – 161.11; MNiSW – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2010, vol. 19, nr 1, January-February, p. 99–104

Publication type: original article

Language: English

Human Pim-2 Gene Expression in Acute Myeloid and Acute Lymphoblastic Leukemia Patients and Complete Remission

Ekspresja genu hPIM-2 u pacjentów chorych na ostrą białaczkę szpikową i limfoblastyczną a remisja całkowita

Katarzyna Kapelko-Słowik1,, Donata Urbaniak-Kujda1,, Dariusz Wołowiec1,, Jarosław Dybko1,, Mirosław Słowik2,, Stanisław Potoczek1,, Kazimierz Kuliczkowski1,

1 Department and Clinic of Haematology, Blood Neoplasms and Bone Marrow Transplantation, Wrocław, Poland

2 Department and Clinic of Ophthalmology, Wrocław, Poland

Abstract

Background. Human Pim-2 is a proto-oncogene that encodes for serine/threonine kinase, which interacts with various signaling molecules. hPim-2 is highly expressed in neoplastic tissues and in leukemic and lymphoma cell lines, which is consistent with its role during oncogenic transformation.
Objectives. The aim of this study was to investigate whether hPim-2 expression is altered in acute myeloblastic leukemia (AML) and acute lymphoblastic leukemia (ALL).
Material and Methods. Thirty-seven patients were included: 22 with AML and 15 with B-cell ALL, aged 21–70 (mean: 41) years. Seventeen patients reached complete remission (CR). Bone marrow samples were collected at the time of diagnosis. Control samples were obtained from 8 healthy donors. hPim-2 expression was analyzed by densitometric RT-PCR analysis.
Results. Expression of hPim-2 in all leukemic patients (n = 37) and in both patient subgroups (AML and ALL) was significantly higher than in the controls (p = 0.00001, p = 0.00009, p = 0.0002, respectively). Patients who reached CR expressed hPim-2 at significantly lower levels than those with primary resistance to chemotherapy (with no CR) (p = 0.01).
Conclusion. Moreover, correlation was found between hPim-2 expression and patient age (r = 0.45; p = 0.005) and white blood cell count (WBC) (r = 0.34; p = 0.04). These data indicate that hPim-2 gene expression is increased in patients with AML and ALL.

Streszczenie

Wprowadzenie. Protoonkogen hPIM-2 koduje kinazę serynowo-treoninową, która odgrywa rolę w przenoszeniu różnych sygnałów. Wysoką ekspresję hPIM-2 stwierdzono w komórkach nowotworowych oraz w białaczkowych i chłoniakowych liniach komórkowych, co wiąże się z jego rolą w procesie transformacji nowotworowej.
Cel pracy. Ocena ekspresji hPIM-2 w komórkach białaczkowych u pacjentów chorych na ostrą białaczkę szpikową (OBS) i limfoblastyczną (OBL).
Materiał i metody. Do badania włączono 37 pacjentów; 22 z OBS i 15 z B komórkową OBL w wieku 21–70 lat (x = 41), 17 pacjentów osiągnęło remisję całkowitą (CR). Szpik kostny był pobierany od pacjentów w chwili rozpoznania. Grupę kontrolną stanowiło 8 zdrowych osób. Analizowano ekspresję hPIM-2 za pomocą testu RT-PCR.
Wyniki. Średnia ekspresja hPIM-2 była istotnie większa w stosunku do grupy kontrolnej we wszystkich badanych białaczkach, a także w podgrupach OBS i OBL (odpowiednio: p = 0,00001, p = 0,00009, p = 0,0002). U pacjentów, którzy uzyskali CR ekspresja ta była istotnie mniejsza niż u pacjentów bez CR (p = 0,01). Obserwowano ponadto, że ekspresja hPIM-2 była istotnie większa w podgrupie pacjentów z OBS w stosunku do pacjentów z OBL (p = 0,04).
Wnioski. Dla całej populacji chorych na ostre białaczki stwierdzono statystycznie istotną dodatnią korelację między ekspresją hPIM-2 a liczbą leukocytów (r = 0,34; p = 0,04) oraz wiekiem chorych (r = 0,45; p = 0,005). Badania własne wykazały, że ekspresja hPIM-2 jest podwyższona u pacjentów z OBS i OBL.

Key words

hPim-2, acute myeloid leukemia, acute lymphoblastic leukemia

Słowa kluczowe

hPim-2, ostra białaczka szpikowa, ostra białaczka limfoblastyczna

References (19)

  1. Breuer ML, Cuypers HT, Berns A: Evidence for the involvement of pim-2, a new common proviral insertion site, in progression of lymphomas. EMBO 1989, 8, 743–748.
  2. Baytel D, Shalom S, Madgar I, Weissenberg R, Don J: The human Pim-2 proto-oncogene and its testicular expression. Biochim Biophys Acta 1998, 1442, 274–285.
  3. Mikkers H, Allen J, Knipscheer P, Romeyn L, Hart A, Vink E, Berns A: High-throughput retroviral tagging to indentify components of specific signaling pathways in cancer. Nat Genet 2002, 32, 153–159.
  4. Reeves R, Spies GA, Kiefer M, Barr PJ, Power M: Primary structure of putative human oncogene, pim-1. Gene 1990, 90, 303–307.
  5. Fox JC, Hammerman PS, Cinalli RM, Master SR, Chodosh LA, Thompson CB: The serine/threonine kinase Pim-2 is transcriptionally regulated apoptotic inhibitor. Gene Dev 2003, 17, 1841–1854.
  6. Clemens MJ, Bushell M, Jeffrey I, Pain VM, Morley SJ: Translation initiation factor modification and the regulation of protein synthesis in apoptotic cells. Cell Death Differ 2000, 7, 603–615.
  7. Hammerman PS, Fox CJ, Brinbaum MJ, Thompson CB: Pim and Akt oncogenes are independent regulators of haematopoietic cell growth and survival. Blood 2005, 105, 11, 4477–4483.
  8. Allen J, Verhoeven E, Domen J, van der Valk M, Berns A: Pim-2 transgene induces lymphoid tumors, exhibiting potent synergy with c-myc. Oncogene 1997, 15, 1133–1141.
  9. Zhang Y, Wang Z, Li X, Magnuson NS: Pim kinase dependent inhibition of c-Myc degradation. Oncogene 2008, 27, 4809–4819.
  10. Dai H, Li R, Wheeler I, Diaz de Vivar A, Frolov A, Tahir S, Agoulnik I, Thompson T, Rowley D, Ayala G: Pim-2 upregulation: biological implications associated with disease progression and perineural invasion in prostate cancer. Prostate 2005, 65, 3, 276–286.
  11. Cohen AM, Grinblat B, Bessler H, Kristt D, Kremer A, Schwartz A, Halperin M, Shalom S, Merkel D, Don J: Increased expression of the hPim-2 gene in human chronic lymphocytic leukaemia and non-Hodgkin lymphoma. Leuk Lymphoma 2004, 45, 5, 951–955.
  12. Amson R, Sigaux F, Przedborski S, Flandrin G, Givol D, Telerman A: The human proto-oncogene product p33pim is expressed during fetal haematopoiesis and in diverse leukaemias. Proc Natl Acad Sci USA, 1989, 86, 8857–8861.
  13. White E: The pims and outs of survival signaling: role for Pim-2 protein kinase in the suppression of apoptosis by cytokines. Genes Dev 2003, 17, 1813–1815.
  14. Yan B, Zemskova M, Holder S, Chin V, Kraft A, Koskinen PJ, Lilly M: The PIM-2 kinase phosphorylates BAD on serine 112 and reverses BAD-induced cell death. J Biol Chem 2003, 14, 278, 46, 45358–45367.
  15. Macdonald A, Campbell DG, Toth R, McLauchlan H, Hastie CJ, Arthur JSC: Pim kinases phosphorylate multiple sites on Bad and promote 14-3-3 binding and dissociation from Bcl-XL. BMC Cell Biol 2006, 7, 1–14.
  16. Dai JM, Zhang SQ, Zhang W, Lin RX, Ji ZZ, Wang SQ: Antisense oligodeoxynucleotides targeting the serine/ threonine kinase Pim-2 inhibited proliferation of DU-145 cells. Acta Pharmacol Sin 2005, 26, 3, 64–68.
  17. Gong J, Wang J, Ren K, Liu C, Li B, Shi Y: Serine/threonine kinase Pim-2 promotes liver tumorigenesis induction through mediating survival and preventing apoptosis of liver cell. J Surg Res 2008, 10.1016/j.jss.2008.03.033.
  18. Zhang SQ, Du QY, Ying Y, Ji ZZ, Wang SQ: Polymerase synthesis and potential interference of a small-interfering RNA targeting hPIM-2. World J Gastroenterol 2004, 10, 18, 2557–2660.
  19. Adam M, Pogacic V, Bendit M, Chappuis R, Nawijn M,Duyster J, Fox CJ, Thompson CB, Cools J, Schwaller J: Targeting PIM kinases impairs survival of haematopoietic cells transformed by kinase inhibitor-sensitive and kinase inhibitor-resistant forms of Fms-like tyrosine kinase 3 and BCR/ABL. Cancer Res 2006, 66, 7, 3828–3835.
© Wroclaw Medical University