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Plasma matrix metalloprotease 9 correlates with blood lymphocytosis, leukemic cell invasiveness, and prognosis in B-cell chronic lymphocytic leukemia.

Abstract The complex biology underlying chronic lymphocytic leukemia cell migration and tissue invasiveness is not yet completely understood and might provide novel predictive markers and therapeutic targets. A total of 36 patients out of treatment from at least 3 months were enrolled and followed up for a median period of 44.2 months (range: 4.4-99.2). Matrix metalloprotease 9 and tissue inhibitor of metalloproteases 1 plasma levels and production/release from lymphoid cells were measured by zymography and enzyme-linked immunosorbent assay (ELISA) analysis. Malignant and normal lymphocyte mobility and matrix-degradation capability were studied using a Boyden chamber system, with and without autologous plasma. Free matrix metalloprotease 9 plasma levels were related with blood lymphocytosis, especially in more advanced stages (p = 0.003), and higher concentrations were associated with an increased disease progression risk (hazard ratio = 9.0, 95% confidence interval = 1.5-13.8). Leukemic cells expressed and secreted very little matrix metalloprotease 9. On the contrary, normal lymphocytes derived from the same leukemic patients showed matrix metalloprotease 9 intracellular levels that were lower in subjects with higher blood lymphocytosis (p = 0.024) and more advanced stages (p = 0.03); the released quantities were inversely associated with matrix metalloprotease 9 plasma concentrations (p = 0.035). Leukemic cells had a reduced spontaneous mobility and matrix-degradation capability that were stimulated by autologous plasma (p = 0.001) and normal lymphocytes (p = 0.005), respectively. Matrix metalloprotease 9 affected cell invasiveness depending on concentration and disease stage. In conclusion, chronic lymphocytic leukemia cells have a reduced mobility, matrix-degradation capability, and matrix metalloprotease 9 production compared to their own autologous normal lymphocytes. They are exposed to matrix metalloprotease 9 of prevalently systemic origin whose higher levels are associated with both leukemic and normal lymphocyte accumulation in the peripheral blood and have a negative prognostic value.
PMID
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Increased serum levels of matrix metalloproteinase-9 predict clinical outcome of patients with early B-cell chronic lymphocytic leukaemia.

Authors

Mayor MeshTerms
Keywords

Chronic lymphocitic leukemia

cell trafficking

matrix metalloproteinases

prognosis

Journal Title tumour biology : the journal of the international society for oncodevelopmental biology and medicine
Publication Year Start




PMID- 28240053
OWN - NLM
STAT- MEDLINE
DA  - 20170227
DCOM- 20170308
LR  - 20170308
IS  - 1423-0380 (Electronic)
IS  - 1010-4283 (Linking)
VI  - 39
IP  - 2
DP  - 2017 Feb
TI  - Plasma matrix metalloprotease 9 correlates with blood lymphocytosis, leukemic
      cell invasiveness, and prognosis in B-cell chronic lymphocytic leukemia.
PG  - 1010428317694325
LID - 10.1177/1010428317694325 [doi]
AB  - The complex biology underlying chronic lymphocytic leukemia cell migration and
      tissue invasiveness is not yet completely understood and might provide novel
      predictive markers and therapeutic targets. A total of 36 patients out of
      treatment from at least 3 months were enrolled and followed up for a median
      period of 44.2 months (range: 4.4-99.2). Matrix metalloprotease 9 and tissue
      inhibitor of metalloproteases 1 plasma levels and production/release from
      lymphoid cells were measured by zymography and enzyme-linked immunosorbent assay 
      (ELISA) analysis. Malignant and normal lymphocyte mobility and matrix-degradation
      capability were studied using a Boyden chamber system, with and without
      autologous plasma. Free matrix metalloprotease 9 plasma levels were related with 
      blood lymphocytosis, especially in more advanced stages (p = 0.003), and higher
      concentrations were associated with an increased disease progression risk (hazard
      ratio = 9.0, 95% confidence interval = 1.5-13.8). Leukemic cells expressed and
      secreted very little matrix metalloprotease 9. On the contrary, normal
      lymphocytes derived from the same leukemic patients showed matrix metalloprotease
      9 intracellular levels that were lower in subjects with higher blood
      lymphocytosis (p = 0.024) and more advanced stages (p = 0.03); the released
      quantities were inversely associated with matrix metalloprotease 9 plasma
      concentrations (p = 0.035). Leukemic cells had a reduced spontaneous mobility and
      matrix-degradation capability that were stimulated by autologous plasma (p =
      0.001) and normal lymphocytes (p = 0.005), respectively. Matrix metalloprotease 9
      affected cell invasiveness depending on concentration and disease stage. In
      conclusion, chronic lymphocytic leukemia cells have a reduced mobility,
      matrix-degradation capability, and matrix metalloprotease 9 production compared
      to their own autologous normal lymphocytes. They are exposed to matrix
      metalloprotease 9 of prevalently systemic origin whose higher levels are
      associated with both leukemic and normal lymphocyte accumulation in the
      peripheral blood and have a negative prognostic value.
FAU - Gusella, Milena
AU  - Gusella M
AD  - 1 Department of Oncology, Azienda ULSS 18 Rovigo, Rovigo, Italy.
FAU - Bolzonella, Caterina
AU  - Bolzonella C
AD  - 1 Department of Oncology, Azienda ULSS 18 Rovigo, Rovigo, Italy.
FAU - Paolini, Rossella
AU  - Paolini R
AD  - 2 Department of Medicine, Azienda ULSS 18 Rovigo, Rovigo, Italy.
FAU - Rodella, Elisabetta
AU  - Rodella E
AD  - 2 Department of Medicine, Azienda ULSS 18 Rovigo, Rovigo, Italy.
FAU - Bertolaso, Laura
AU  - Bertolaso L
AD  - 1 Department of Oncology, Azienda ULSS 18 Rovigo, Rovigo, Italy.
FAU - Scipioni, Cinzia
AU  - Scipioni C
AD  - 3 Department of Transfusion Medicine, Azienda ULSS 18 Rovigo, Rovigo, Italy.
FAU - Bellini, Silvia
AU  - Bellini S
AD  - 3 Department of Transfusion Medicine, Azienda ULSS 18 Rovigo, Rovigo, Italy.
FAU - Cuneo, Antonio
AU  - Cuneo A
AD  - 4 Department of Medical Sciences, Section of Hematology, University of Ferrara,
      Ferrara, Italy.
FAU - Pasini, Felice
AU  - Pasini F
AD  - 1 Department of Oncology, Azienda ULSS 18 Rovigo, Rovigo, Italy.
FAU - Ramazzina, Emilio
AU  - Ramazzina E
AD  - 2 Department of Medicine, Azienda ULSS 18 Rovigo, Rovigo, Italy.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Tumour Biol
JT  - Tumour biology : the journal of the International Society for Oncodevelopmental
      Biology and Medicine
JID - 8409922
RN  - 0 (TIMP1 protein, human)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - EC 3.4.24.35 (MMP9 protein, human)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Cell Movement/physiology
MH  - Female
MH  - Humans
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/blood/*enzymology/pathology
MH  - Lymphocytosis/blood/*enzymology/pathology
MH  - Male
MH  - Matrix Metalloproteinase 9/*blood
MH  - Middle Aged
MH  - Neoplasm Invasiveness
MH  - Prognosis
MH  - Tissue Inhibitor of Metalloproteinase-1/blood
OTO - NOTNLM
OT  - Chronic lymphocitic leukemia
OT  - cell trafficking
OT  - matrix metalloproteinases
OT  - prognosis
EDAT- 2017/02/28 06:00
MHDA- 2017/03/09 06:00
CRDT- 2017/02/28 06:00
AID - 10.1177/1010428317694325 [doi]
PST - ppublish
SO  - Tumour Biol. 2017 Feb;39(2):1010428317694325. doi: 10.1177/1010428317694325.

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