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Immunophenotyping of Waldenströms macroglobulinemia cell lines reveals distinct patterns of surface antigen expression: potential biological and therapeutic implications.

Paulus A, Chitta KS, Wallace PK, Advani PP, Akhtar S, Kuranz-Blake M, Ailawadhi S, Chanan-Khan AA - PLoS ONE (2015)

Bottom Line: RPCI-WM1 cells demonstrated decreased expression of CD19, CD20, and CD23 with enhanced expression of CD28, CD38 and CD184, antigens that were differentially expressed on BCWM.1 and MWCL-1 cells.Due to increased expression of CD184/CXCR4 and CD38, RPCI-WM1 represents a valuable model in which to study the effects anti-CXCR4 or anti-CD38 targeted therapies that are actively being developed for treatment of hematologic cancers.Our analysis defines the utility of the most commonly employed WM cell lines as based on their immunophenotype profiles, highlighting unique differences that can be further studied for therapeutic exploit.

View Article: PubMed Central - PubMed

Affiliation: Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida, United States of America.

ABSTRACT
Waldenströms macroglobulinemia (WM) is a subtype of Non-Hodgkin's lymphoma in which the tumor cell population is markedly heterogeneous, consisting of immunoglobulin-M secreting B-lymphocytes, plasmacytoid lymphocytes and plasma cells. Due to rarity of disease and scarcity of reliable preclinical models, many facets of WM molecular and phenotypic architecture remain incompletely understood. Currently, there are 3 human WM cell lines that are routinely used in experimental studies, namely, BCWM.1, MWCL-1 and RPCI-WM1. During establishment of RPCI-WM1, we observed loss of the CD19 and CD20 antigens, which are typically present on WM cells. Intrigued by this observation and in an effort to better define the immunophenotypic makeup of this cell line, we conducted a more comprehensive analysis for the presence or absence of other cell surface antigens that are present on the RPCI-WM1 model, as well as those on the two other WM cell lines, BCWM.1 and MWCL-1. We examined expression of 65 extracellular and 4 intracellular antigens, comprising B-cell, plasma cell, T-cell, NK-cell, myeloid and hematopoietic stem cell surface markers by flow cytometry analysis. RPCI-WM1 cells demonstrated decreased expression of CD19, CD20, and CD23 with enhanced expression of CD28, CD38 and CD184, antigens that were differentially expressed on BCWM.1 and MWCL-1 cells. Due to increased expression of CD184/CXCR4 and CD38, RPCI-WM1 represents a valuable model in which to study the effects anti-CXCR4 or anti-CD38 targeted therapies that are actively being developed for treatment of hematologic cancers. Overall, differences in surface antigen expression across the 3 cell lines may reflect the tumor clone population predominant in the index patients, from whom the cell lines were developed. Our analysis defines the utility of the most commonly employed WM cell lines as based on their immunophenotype profiles, highlighting unique differences that can be further studied for therapeutic exploit.

No MeSH data available.


Related in: MedlinePlus

Presence of stem-cell markers on RPCI-WM1.A total of 8 surface antigens that are typically expressed on the surface of stem cells were examined. Notably, more than 90% of RPCI-WM1 cells gated were CD110+low and CXCR4/CD184+low. A comparison of these and the remaining stem-cell antigens in BCWM.1 and MWCL-1 cell lines is presented in Table 4.
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pone.0122338.g004: Presence of stem-cell markers on RPCI-WM1.A total of 8 surface antigens that are typically expressed on the surface of stem cells were examined. Notably, more than 90% of RPCI-WM1 cells gated were CD110+low and CXCR4/CD184+low. A comparison of these and the remaining stem-cell antigens in BCWM.1 and MWCL-1 cell lines is presented in Table 4.

Mentions: Tumor cells from many diseases, including B-cell cancers, have been found to express surface markers that are more typically used to characteristic hematopoietic stem cells. As such, we first examined in RPCI-WM1, the expression of 8 stem cell markers whose expression has been shown on lymphoid or myeloid lineage cancers (Fig 4).[24–30] RPCI-WM1 cells were noted to be negative for CD34, 90, 105, 111, 117 and 202b while being positive (>95% of gated cells) for CD110 and CD184 (CXCR4). Both markers were lowly expressed with CD184 fluorescence being higher (MESF 19,1152) than CD110 (MESF 6,712). Expression of these antigens, as well as the 6 others that RPCI-WM1 cells did not express, were quantified in BCWM.1 and MWCL-1 cells also. While CD184 was expressed on >80% of BCWM.1 cells, its surface density was low (MESF 9,618). Contrastingly, CD184 was virtually absent on MWCL-1 cells (8.8% cells gated, MESF 740.5). We did not observe any expression of CD34, 90 or 202b on either cell line, however, CD105+low expression was found on approximately 79% of MWCL-1 cells but virtually absent, on BCWM.1, similar to RPCI-WM1. Also, CD111 was lowly expressed on >60% of BCWM.1 (MESF 4,594.6) and MWCL-1 tumor cells (MESF 4,335) in contrast to 5.2% of RPCI-WM1 (MESF 1,470.4) (see Table 4).


Immunophenotyping of Waldenströms macroglobulinemia cell lines reveals distinct patterns of surface antigen expression: potential biological and therapeutic implications.

Paulus A, Chitta KS, Wallace PK, Advani PP, Akhtar S, Kuranz-Blake M, Ailawadhi S, Chanan-Khan AA - PLoS ONE (2015)

Presence of stem-cell markers on RPCI-WM1.A total of 8 surface antigens that are typically expressed on the surface of stem cells were examined. Notably, more than 90% of RPCI-WM1 cells gated were CD110+low and CXCR4/CD184+low. A comparison of these and the remaining stem-cell antigens in BCWM.1 and MWCL-1 cell lines is presented in Table 4.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390194&req=5

pone.0122338.g004: Presence of stem-cell markers on RPCI-WM1.A total of 8 surface antigens that are typically expressed on the surface of stem cells were examined. Notably, more than 90% of RPCI-WM1 cells gated were CD110+low and CXCR4/CD184+low. A comparison of these and the remaining stem-cell antigens in BCWM.1 and MWCL-1 cell lines is presented in Table 4.
Mentions: Tumor cells from many diseases, including B-cell cancers, have been found to express surface markers that are more typically used to characteristic hematopoietic stem cells. As such, we first examined in RPCI-WM1, the expression of 8 stem cell markers whose expression has been shown on lymphoid or myeloid lineage cancers (Fig 4).[24–30] RPCI-WM1 cells were noted to be negative for CD34, 90, 105, 111, 117 and 202b while being positive (>95% of gated cells) for CD110 and CD184 (CXCR4). Both markers were lowly expressed with CD184 fluorescence being higher (MESF 19,1152) than CD110 (MESF 6,712). Expression of these antigens, as well as the 6 others that RPCI-WM1 cells did not express, were quantified in BCWM.1 and MWCL-1 cells also. While CD184 was expressed on >80% of BCWM.1 cells, its surface density was low (MESF 9,618). Contrastingly, CD184 was virtually absent on MWCL-1 cells (8.8% cells gated, MESF 740.5). We did not observe any expression of CD34, 90 or 202b on either cell line, however, CD105+low expression was found on approximately 79% of MWCL-1 cells but virtually absent, on BCWM.1, similar to RPCI-WM1. Also, CD111 was lowly expressed on >60% of BCWM.1 (MESF 4,594.6) and MWCL-1 tumor cells (MESF 4,335) in contrast to 5.2% of RPCI-WM1 (MESF 1,470.4) (see Table 4).

Bottom Line: RPCI-WM1 cells demonstrated decreased expression of CD19, CD20, and CD23 with enhanced expression of CD28, CD38 and CD184, antigens that were differentially expressed on BCWM.1 and MWCL-1 cells.Due to increased expression of CD184/CXCR4 and CD38, RPCI-WM1 represents a valuable model in which to study the effects anti-CXCR4 or anti-CD38 targeted therapies that are actively being developed for treatment of hematologic cancers.Our analysis defines the utility of the most commonly employed WM cell lines as based on their immunophenotype profiles, highlighting unique differences that can be further studied for therapeutic exploit.

View Article: PubMed Central - PubMed

Affiliation: Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida, United States of America.

ABSTRACT
Waldenströms macroglobulinemia (WM) is a subtype of Non-Hodgkin's lymphoma in which the tumor cell population is markedly heterogeneous, consisting of immunoglobulin-M secreting B-lymphocytes, plasmacytoid lymphocytes and plasma cells. Due to rarity of disease and scarcity of reliable preclinical models, many facets of WM molecular and phenotypic architecture remain incompletely understood. Currently, there are 3 human WM cell lines that are routinely used in experimental studies, namely, BCWM.1, MWCL-1 and RPCI-WM1. During establishment of RPCI-WM1, we observed loss of the CD19 and CD20 antigens, which are typically present on WM cells. Intrigued by this observation and in an effort to better define the immunophenotypic makeup of this cell line, we conducted a more comprehensive analysis for the presence or absence of other cell surface antigens that are present on the RPCI-WM1 model, as well as those on the two other WM cell lines, BCWM.1 and MWCL-1. We examined expression of 65 extracellular and 4 intracellular antigens, comprising B-cell, plasma cell, T-cell, NK-cell, myeloid and hematopoietic stem cell surface markers by flow cytometry analysis. RPCI-WM1 cells demonstrated decreased expression of CD19, CD20, and CD23 with enhanced expression of CD28, CD38 and CD184, antigens that were differentially expressed on BCWM.1 and MWCL-1 cells. Due to increased expression of CD184/CXCR4 and CD38, RPCI-WM1 represents a valuable model in which to study the effects anti-CXCR4 or anti-CD38 targeted therapies that are actively being developed for treatment of hematologic cancers. Overall, differences in surface antigen expression across the 3 cell lines may reflect the tumor clone population predominant in the index patients, from whom the cell lines were developed. Our analysis defines the utility of the most commonly employed WM cell lines as based on their immunophenotype profiles, highlighting unique differences that can be further studied for therapeutic exploit.

No MeSH data available.


Related in: MedlinePlus