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Gene expression profiling of hairy cell leukemia reveals a phenotype related to memory B cells with altered expression of chemokine and adhesion receptors.

Basso K, Liso A, Tiacci E, Benedetti R, Pulsoni A, Foa R, Di Raimondo F, Ambrosetti A, Califano A, Klein U, Dalla Favera R, Falini B - J. Exp. Med. (2004)

Bottom Line: Comparison with the gene expression profiles of purified normal B cell subpopulations, including germinal center (GC), pre-GC (naive), and post-GC (memory) B cells, shows that HCL cells are more related to memory cells, suggesting a derivation from this B cell population.Notably, when compared with memory cells, HCL cells displayed a remarkable conservation in proliferation, apoptosis, and DNA metabolism programs, whereas they appeared significantly altered in the expression of genes controlling cell adhesion and response to chemokines.Finally, these analyses have identified several genes that are specifically expressed in HCL and whose expression was confirmed at the protein level by immunocytochemical analysis of primary HCL cases.

View Article: PubMed Central - PubMed

Affiliation: Institute of Hematology, Policlinico Monteluce, Perugia 06100, Italy.

ABSTRACT
Hairy cell leukemia (HCL) is a chronic B cell malignancy characterized by the diffuse infiltration of bone marrow and spleen by cells displaying a typical "hairy" morphology. However, the nature of the HCL phenotype and its relationship to normal B cells and to other lymphoma subtypes remains unclear. Using gene expression profiling, we show here that HCL displays a homogeneous pattern of gene expression, which is clearly distinct from that of other B cell non-Hodgkin lymphomas. Comparison with the gene expression profiles of purified normal B cell subpopulations, including germinal center (GC), pre-GC (naive), and post-GC (memory) B cells, shows that HCL cells are more related to memory cells, suggesting a derivation from this B cell population. Notably, when compared with memory cells, HCL cells displayed a remarkable conservation in proliferation, apoptosis, and DNA metabolism programs, whereas they appeared significantly altered in the expression of genes controlling cell adhesion and response to chemokines. Finally, these analyses have identified several genes that are specifically expressed in HCL and whose expression was confirmed at the protein level by immunocytochemical analysis of primary HCL cases. These results have biological implications relevant to the pathogenesis of this malignancy as well as clinical implications for its diagnosis and therapy.

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(top left, DBA44) BM biopsy from patient 5 showing massive infiltration by DBA44+ hairy cells; the arrow indicates rare residual hemopoietic precursors. (T) A bone trabecula (APAAP; 800×). (top middle, DBA44) Cytocentrifuge preparation (patient 3) showing strong surface positivity of HCL cells for DBA44 (arrow, APAAP; 800×). (Na+ CP, I) Cytospin (patient 3). Positivity for Na+ channel, type I, is mainly seen on the surface membrane (arrow). A negative lymphoid cell (arrowhead, APAAP; 800×). (FLT3) Cytospin (patient 3). Labeling of leukemic cells for FLT3 is mainly seen on the cell surface (arrow). A negative normal residual lymphocyte (arrowhead, APAAP; 800×). (CD63 and SYND-3) Cytospins (patient 3). Expression of CD63 and Syndecan-3 expression are mainly cytoplasmic (arrow, microgranular) and perinuclear (arrow), respectively (APAAP; 800×). (FGF2) BM biopsy (paraffin section) from patient 4. HCL cells show strong nuclear and cytoplasmic positivity for FGF2 (arrow, bFGF), whereas residual hemopoietic precursors are negative (arrowhead, APAAP; 800×). (Annexin I) BM biopsy (patient 4). Leukemic cells are strongly positive for annexin I (arrow). Positivity is mainly seen in the cytoplasm and surface, whereas nuclei are negative or faintly positive. An island of annexin 1–negative residual erythroid precursors is shown (APAAP; 800×). (TIMP1) Liver biopsy (paraffin section) from patient 3 showing typical infiltration of hepatic sinusoids by TIMP1+ leukemic hairy cells (APAAP; 800×).
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fig5: (top left, DBA44) BM biopsy from patient 5 showing massive infiltration by DBA44+ hairy cells; the arrow indicates rare residual hemopoietic precursors. (T) A bone trabecula (APAAP; 800×). (top middle, DBA44) Cytocentrifuge preparation (patient 3) showing strong surface positivity of HCL cells for DBA44 (arrow, APAAP; 800×). (Na+ CP, I) Cytospin (patient 3). Positivity for Na+ channel, type I, is mainly seen on the surface membrane (arrow). A negative lymphoid cell (arrowhead, APAAP; 800×). (FLT3) Cytospin (patient 3). Labeling of leukemic cells for FLT3 is mainly seen on the cell surface (arrow). A negative normal residual lymphocyte (arrowhead, APAAP; 800×). (CD63 and SYND-3) Cytospins (patient 3). Expression of CD63 and Syndecan-3 expression are mainly cytoplasmic (arrow, microgranular) and perinuclear (arrow), respectively (APAAP; 800×). (FGF2) BM biopsy (paraffin section) from patient 4. HCL cells show strong nuclear and cytoplasmic positivity for FGF2 (arrow, bFGF), whereas residual hemopoietic precursors are negative (arrowhead, APAAP; 800×). (Annexin I) BM biopsy (patient 4). Leukemic cells are strongly positive for annexin I (arrow). Positivity is mainly seen in the cytoplasm and surface, whereas nuclei are negative or faintly positive. An island of annexin 1–negative residual erythroid precursors is shown (APAAP; 800×). (TIMP1) Liver biopsy (paraffin section) from patient 3 showing typical infiltration of hepatic sinusoids by TIMP1+ leukemic hairy cells (APAAP; 800×).

Mentions: The expression in HCL cells was confirmed for the following proteins: FGF2 (bFGF), annexin 1, CD135 (FLT3), Na+ CP type I (SCN1B), CD63, Syndecan-3, TIMP1 (Fig. 5) as well as IL-3Rα, cyclin D1, FGFR1, GAS7, EPB4.1L2, β-actin, CPVL, β-arrestin-2, insulin-like growth factor binding protein (IGFBP3), MYF6 (Herculin), protein tyrosine phosphatase receptor μ (PTPRμ), Synaptotagmin 1, plexin-C1, TIMP4, and β-2-microglobulin (not depicted). Thus, these results indicate that the HCL-specific overexpression of genes detected by gene expression profiling is associated with the overexpression of the corresponding protein for all genes tested.


Gene expression profiling of hairy cell leukemia reveals a phenotype related to memory B cells with altered expression of chemokine and adhesion receptors.

Basso K, Liso A, Tiacci E, Benedetti R, Pulsoni A, Foa R, Di Raimondo F, Ambrosetti A, Califano A, Klein U, Dalla Favera R, Falini B - J. Exp. Med. (2004)

(top left, DBA44) BM biopsy from patient 5 showing massive infiltration by DBA44+ hairy cells; the arrow indicates rare residual hemopoietic precursors. (T) A bone trabecula (APAAP; 800×). (top middle, DBA44) Cytocentrifuge preparation (patient 3) showing strong surface positivity of HCL cells for DBA44 (arrow, APAAP; 800×). (Na+ CP, I) Cytospin (patient 3). Positivity for Na+ channel, type I, is mainly seen on the surface membrane (arrow). A negative lymphoid cell (arrowhead, APAAP; 800×). (FLT3) Cytospin (patient 3). Labeling of leukemic cells for FLT3 is mainly seen on the cell surface (arrow). A negative normal residual lymphocyte (arrowhead, APAAP; 800×). (CD63 and SYND-3) Cytospins (patient 3). Expression of CD63 and Syndecan-3 expression are mainly cytoplasmic (arrow, microgranular) and perinuclear (arrow), respectively (APAAP; 800×). (FGF2) BM biopsy (paraffin section) from patient 4. HCL cells show strong nuclear and cytoplasmic positivity for FGF2 (arrow, bFGF), whereas residual hemopoietic precursors are negative (arrowhead, APAAP; 800×). (Annexin I) BM biopsy (patient 4). Leukemic cells are strongly positive for annexin I (arrow). Positivity is mainly seen in the cytoplasm and surface, whereas nuclei are negative or faintly positive. An island of annexin 1–negative residual erythroid precursors is shown (APAAP; 800×). (TIMP1) Liver biopsy (paraffin section) from patient 3 showing typical infiltration of hepatic sinusoids by TIMP1+ leukemic hairy cells (APAAP; 800×).
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fig5: (top left, DBA44) BM biopsy from patient 5 showing massive infiltration by DBA44+ hairy cells; the arrow indicates rare residual hemopoietic precursors. (T) A bone trabecula (APAAP; 800×). (top middle, DBA44) Cytocentrifuge preparation (patient 3) showing strong surface positivity of HCL cells for DBA44 (arrow, APAAP; 800×). (Na+ CP, I) Cytospin (patient 3). Positivity for Na+ channel, type I, is mainly seen on the surface membrane (arrow). A negative lymphoid cell (arrowhead, APAAP; 800×). (FLT3) Cytospin (patient 3). Labeling of leukemic cells for FLT3 is mainly seen on the cell surface (arrow). A negative normal residual lymphocyte (arrowhead, APAAP; 800×). (CD63 and SYND-3) Cytospins (patient 3). Expression of CD63 and Syndecan-3 expression are mainly cytoplasmic (arrow, microgranular) and perinuclear (arrow), respectively (APAAP; 800×). (FGF2) BM biopsy (paraffin section) from patient 4. HCL cells show strong nuclear and cytoplasmic positivity for FGF2 (arrow, bFGF), whereas residual hemopoietic precursors are negative (arrowhead, APAAP; 800×). (Annexin I) BM biopsy (patient 4). Leukemic cells are strongly positive for annexin I (arrow). Positivity is mainly seen in the cytoplasm and surface, whereas nuclei are negative or faintly positive. An island of annexin 1–negative residual erythroid precursors is shown (APAAP; 800×). (TIMP1) Liver biopsy (paraffin section) from patient 3 showing typical infiltration of hepatic sinusoids by TIMP1+ leukemic hairy cells (APAAP; 800×).
Mentions: The expression in HCL cells was confirmed for the following proteins: FGF2 (bFGF), annexin 1, CD135 (FLT3), Na+ CP type I (SCN1B), CD63, Syndecan-3, TIMP1 (Fig. 5) as well as IL-3Rα, cyclin D1, FGFR1, GAS7, EPB4.1L2, β-actin, CPVL, β-arrestin-2, insulin-like growth factor binding protein (IGFBP3), MYF6 (Herculin), protein tyrosine phosphatase receptor μ (PTPRμ), Synaptotagmin 1, plexin-C1, TIMP4, and β-2-microglobulin (not depicted). Thus, these results indicate that the HCL-specific overexpression of genes detected by gene expression profiling is associated with the overexpression of the corresponding protein for all genes tested.

Bottom Line: Comparison with the gene expression profiles of purified normal B cell subpopulations, including germinal center (GC), pre-GC (naive), and post-GC (memory) B cells, shows that HCL cells are more related to memory cells, suggesting a derivation from this B cell population.Notably, when compared with memory cells, HCL cells displayed a remarkable conservation in proliferation, apoptosis, and DNA metabolism programs, whereas they appeared significantly altered in the expression of genes controlling cell adhesion and response to chemokines.Finally, these analyses have identified several genes that are specifically expressed in HCL and whose expression was confirmed at the protein level by immunocytochemical analysis of primary HCL cases.

View Article: PubMed Central - PubMed

Affiliation: Institute of Hematology, Policlinico Monteluce, Perugia 06100, Italy.

ABSTRACT
Hairy cell leukemia (HCL) is a chronic B cell malignancy characterized by the diffuse infiltration of bone marrow and spleen by cells displaying a typical "hairy" morphology. However, the nature of the HCL phenotype and its relationship to normal B cells and to other lymphoma subtypes remains unclear. Using gene expression profiling, we show here that HCL displays a homogeneous pattern of gene expression, which is clearly distinct from that of other B cell non-Hodgkin lymphomas. Comparison with the gene expression profiles of purified normal B cell subpopulations, including germinal center (GC), pre-GC (naive), and post-GC (memory) B cells, shows that HCL cells are more related to memory cells, suggesting a derivation from this B cell population. Notably, when compared with memory cells, HCL cells displayed a remarkable conservation in proliferation, apoptosis, and DNA metabolism programs, whereas they appeared significantly altered in the expression of genes controlling cell adhesion and response to chemokines. Finally, these analyses have identified several genes that are specifically expressed in HCL and whose expression was confirmed at the protein level by immunocytochemical analysis of primary HCL cases. These results have biological implications relevant to the pathogenesis of this malignancy as well as clinical implications for its diagnosis and therapy.

Show MeSH
Related in: MedlinePlus