Waldenström's macroglobulinemia pathophysiology: Difference between revisions

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==Overview==
==Overview==
== Pathogenesis ==
== Pathogenesis ==
It is due to the effects of the [[IgM]] [[paraprotein]], which may cause [[autoimmune]] phenomenon or [[cryoglobulinemia]].  Other symptoms of WM are due to the [[hyperviscosity syndrome]], which is present in 6-20% of patients.This is attributed to the [[IgM]] monoclonal protein increasing the viscosity of the blood.
Waldenström's macroglobulinemia arises from B lymphocytes, which are involved in humoral immunity.  
==Genetics==
==Genetics==
Although believed to be a sporadic disease, studies have shown increased susceptibility within families, indicating a genetic component.<ref>{{Cite journal| last1 = McMaster | first1 = M.| title = Familial Waldenstrom's macroglobulinemia| journal = Seminars in oncology| volume = 30| issue = 2| pages = 146–152| year = 2003| pmid = 12720125| doi = 10.1053/sonc.2003.50063}}</ref><ref>{{Cite journal| last1 = McMaster | first1 = M.| last2 = Goldin | first2 = L.| last3 = Bai | first3 = Y.| last4 = Ter-Minassian | first4 = M.| last5 = Boehringer | first5 = S.| last6 = Giambarresi | first6 = T.| last7 = Vasquez | first7 = L.| last8 = Tucker | first8 = M.| title = Genomewide linkage screen for Waldenstrom macroglobulinemia susceptibility loci in high-risk families| journal = American Journal of Human Genetics| volume = 79| issue = 4| pages = 695–701| year = 2006| pmid = 16960805| pmc = 1592553| doi = 10.1086/507687}}</ref>  A mutation in gene MYD88 has been found to occur frequently in patients.<ref>{{Cite journal | last1 = Treon | first1 = S. P. | last2 = Xu | first2 = L. | last3 = Yang | first3 = G. | last4 = Zhou | first4 = Y. | last5 = Liu | first5 = X. | last6 = Cao | first6 = Y. | last7 = Sheehy | first7 = P. | last8 = Manning | first8 = R. J. | last9 = Patterson | first9 = C. J. | last10 = Tripsas | doi = 10.1056/NEJMoa1200710 | first10 = C. | last11 = Arcaini | first11 = L. | last12 = Pinkus | first12 = G. S. | last13 = Rodig | first13 = S. J. | last14 = Sohani | first14 = A. R. | last15 = Harris | first15 = N. L. | last16 = Laramie | first16 = J. M. | last17 = Skifter | first17 = D. A. | last18 = Lincoln | first18 = S. E. | last19 = Hunter | first19 = Z. R. | title = MYD88 L265P Somatic Mutation in Waldenström's Macroglobulinemia | journal = New England Journal of Medicine | volume = 367 | issue = 9 | pages = 826–833 | year = 2012 | pmid = 22931316 | pmc = }}</ref>  WM cells show only minimal changes in [[cytogenetic]] and gene expression profiling|gene expression studies.  Their miRNA signature however differs from their normal counterpart. It is therefore believed that [[Epigenetics|epigenetic]] modifications play a crucial role in the disease.<ref>{{Cite journal | doi = 10.1186/1756-8722-3-38 | last1 = Sacco | first1 = A. | last2 = Issa | first2 = G. C. | last3 = Zhang | first3 = Y. | last4 = Liu | first4 = Y. | last5 = Maiso | first5 = P. | last6 = Ghobrial | first6 = I. M. | last7 = Roccaro | first7 = A. M. | title = Epigenetic modifications as key regulators of Waldenstrom's Macroglobulinemia biology | journal = Journal of Hematology & Oncology | volume = 3 | pages = 38 | year = 2010 | pmid = 20929526 | pmc = 2964547}}</ref>
[[Comparative genomic hybridization]] identified the following [[chromosomal abnormalities]]: deletions of 6q23 and 13q14, and gains of 3q13-q28, 6p and 18q.<ref>{{Cite journal| last1 = Braggio | first1 = E.| last2 = Keats | first2 = J. J.| last3 = Leleu | first3 = X.| last4 = Van Wier | first4 = S. V.| last5 = Jimenez-Zepeda | first5 = V. H.| last6 = Schop | first6 = R. F. J.| last7 = Chesi | first7 = M.| last8 = Barrett | first8 = M.| last9 = Stewart | first9 = A. K.| last10 = Dogan | first10 = A.| last11 = Bergsagel | first11 = P. L.| last12 = Ghobrial | first12 = I. M.| last13 = Fonseca | first13 = R.| title = High-Resolution Genomic Analysis in Waldenström's Macroglobulinemia Identifies Disease-Specific and Common Abnormalities with Marginal Zone Lymphomas| journal = Clinical Lymphoma, Myeloma & Leukemia| volume = 9| issue = 1| pages = 39–42| year = 2009| pmid = 19362969| pmc = 3646570| doi = 10.3816/CLM.2009.n.009}}</ref> [[FGFR3]] is overexpressed.<ref>{{Cite journal | last1 = Azab | first1 = A. K. | last2 = Azab | first2 = F. | last3 = Quang | first3 = P. | last4 = Maiso | first4 = P. | last5 = Sacco | first5 = B. | last6 = Ngo | first6 = A. | last7 = Liu | first7 = H. T. | last8 = Zhang | first8 = Y. | last9 = Morgan | first9 = Y. | last10 = Roccaro | first10 = A. M. | last11 = Ghobrial | first11 = I. M. | title = FGFR3 is overexpressed Waldenstrom macroglobulinemia and its inhibition by Dovitinib induces apoptosis, and overcomes stroma-induced proliferation | doi = 10.1158/1078-0432.CCR-10-2772 | journal = Clinical Cancer Research | year = 2011 | pmid = 21521775 | volume=17 | issue=13 | pages=4389–4399}}</ref>
The following signalling pathways have been implicated:
*[[CD154]]/[[CD40]]<ref>http://www.asco.org/ASCO/Abstracts+&+Virtual+Meeting/Abstracts?&vmview=abst_detail_view&confID=26&abstractID=4297</ref>
*[[Akt]]<ref>{{Cite journal| last1 = Leleu | first1 = X.| last2 = Jia | first2 = X.| last3 = Runnels | first3 = J.| last4 = Ngo | first4 = H.| last5 = Moreau | first5 = A.| last6 = Farag | first6 = M.| last7 = Spencer | first7 = J.| last8 = Pitsillides | first8 = C.| last9 = Hatjiharissi | first9 = E.| last10 = Roccaro | first10 = A.| last11 = O'Sullivan | first11 = G.| last12 = McMillin | first12 = D. W.| last13 = Moreno | first13 = D.| last14 = Kiziltepe | first14 = T.| last15 = Carrasco | first15 = R.| last16 = Treon | first16 = S. P.| last17 = Hideshima | first17 = T.| last18 = Anderson | first18 = K. C.| last19 = Lin | first19 = C. P.| last20 = Ghobrial | first20 = I. M.| title = The Akt pathway regulates survival and homing in Waldenstrom macroglobulinemia| journal = Blood| volume = 110| issue = 13| pages = 4417–4426| year = 2007| pmid = 17761832| pmc = 2234792| doi = 10.1182/blood-2007-05-092098}}</ref>
*[[ubiquitination]], [[p53]] activation, [[cytochrome c]] release<ref>{{Cite journal| last1 = Mensah-Osman | first1 = E.| last2 = Al-Katib | first2 = A.| last3 = Dandashi | first3 = M.| last4 = Mohammad | first4 = R.| title = XK469, a topo IIbeta inhibitor, induces apoptosis in Waldenstrom's macroglobulinemia through multiple pathways| journal = International journal of oncology| volume = 23| issue = 6| pages = 1637–1644| year = 2003| pmid = 14612935 | doi=10.3892/ijo.23.6.1637}}</ref>
*[[NF-κB]]<ref name="PMID 18334673">{{Cite journal| last1 = Leleu | first1 = X.| last2 = Eeckhoute | first2 = J.| last3 = Jia | first3 = X.| last4 = Roccaro | first4 = A.| last5 = Moreau | first5 = A.| last6 = Farag | first6 = M.| last7 = Sacco | first7 = A.| last8 = Ngo | first8 = H.| last9 = Runnels | first9 = J.| last10 = Melhem | first10 = M. R.| last11 = Burwick | first11 = N.| last12 = Azab | first12 = A.| last13 = Azab | first13 = F.| last14 = Hunter | first14 = Z.| last15 = Hatjiharissi | first15 = E.| last16 = Carrasco | first16 = D. R.| last17 = Treon | first17 = S. P.| last18 = Witzig | first18 = T. E.| last19 = Hideshima | first19 = T.| last20 = Brown | first20 = M.| last21 = Anderson | first21 = K. C.| last22 = Ghobrial | first22 = I. M.| title = Targeting NF-kappaB in Waldenstrom macroglobulinemia| journal = Blood| volume = 111| issue = 10| pages = 5068–5077| year = 2008| pmid = 18334673| pmc = 2384134| doi = 10.1182/blood-2007-09-115170}}</ref><ref>{{Cite journal| last1 = Braggio | first1 = E.| last2 = Keats | first2 = J.| last3 = Leleu | first3 = X.| last4 = Van Wier | first4 = S.| last5 = Jimenez-Zepeda | first5 = V.| last6 = Valdez | first6 = R.| last7 = Schop | first7 = R.| last8 = Price-Troska | first8 = T.| last9 = Henderson | first9 = K.| last10 = Sacco | first10 = A.| last11 = Azab | first11 = F.| last12 = Greipp | first12 = P.| last13 = Gertz | first13 = M.| last14 = Hayman | first14 = S.| last15 = Rajkumar | first15 = S. V.| last16 = Carpten | first16 = J.| last17 = Chesi | first17 = M.| last18 = Barrett | first18 = M.| last19 = Stewart | first19 = A. K.| last20 = Dogan | first20 = A.| last21 = Bergsagel | first21 = P. L.| last22 = Ghobrial | first22 = I. M.| last23 = Fonseca | first23 = R.| title = Identification of copy number abnormalities and inactivating mutations in two negative regulators of nuclear factor-kappaB signaling pathways in Waldenstrom's macroglobulinemia| journal = Cancer Research| volume = 69| issue = 8| pages = 3579–3588| year = 2009| pmid = 19351844| pmc = 2782932| doi = 10.1158/0008-5472.CAN-08-3701}}</ref>
*[[Wnt signaling pathway|WNT]]/[[beta-catenin]]<ref>{{Cite journal| last1 = Gutiérrez | first1 = N.| last2 = Ocio | first2 = E.| last3 = De Las Rivas | first3 = J.| last4 = Maiso | first4 = P.| last5 = Delgado | first5 = M.| last6 = Fermiñán | first6 = E.| last7 = Arcos | first7 = M.| last8 = Sánchez | first8 = M.| last9 = Hernández | first9 = J.| last10 = San Miguel | first10 = J. F.| title = Gene expression profiling of B lymphocytes and plasma cells from Waldenström's macroglobulinemia: comparison with expression patterns of the same cell counterparts from chronic lymphocytic leukemia, multiple myeloma and normal individuals| journal = Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K| volume = 21| issue = 3| pages = 541–549| year = 2007| pmid = 17252022| doi = 10.1038/sj.leu.2404520}}</ref>
*mTOR<ref>{{Cite journal| last1 = Burwick | first1 = N.| last2 = Roccaro | first2 = A.| last3 = Leleu | first3 = X.| last4 = Ghobrial | first4 = I.| title = Targeted therapies in Waldenström macroglobulinemia| journal = Current opinion in investigational drugs (London, England : 2000)| volume = 9| issue = 6| pages = 631–637| year = 2008| pmid = 18516762}}</ref>
*[[Extracellular signal-regulated kinases|ERK]]<ref name="PMID 18334673"/>
*[[MAPK]]<ref>{{Cite journal| last1 = Chng | first1 = W.| last2 = Schop | first2 = R.| last3 = Price-Troska | first3 = T.| last4 = Ghobrial | first4 = I.| last5 = Kay | first5 = N.| last6 = Jelinek | first6 = D.| last7 = Gertz | first7 = M.| last8 = Dispenzieri | first8 = A.| last9 = Lacy | first9 = M.| last10 = Kyle | first10 = R. A.| last11 = Greipp | first11 = P. R.| last12 = Tschumper | first12 = R. C.| last13 = Fonseca | first13 = R.| last14 = Bergsagel | first14 = P. L.| title = Gene-expression profiling of Waldenstrom macroglobulinemia reveals a phenotype more similar to chronic lymphocytic leukemia than multiple myeloma| journal = Blood| volume = 108| issue = 8| pages = 2755–2763| year = 2006| pmid = 16804116| pmc = 1895596| doi = 10.1182/blood-2006-02-005488}}</ref>
*[[Bcl-2]]<ref>{{Cite journal| last1 = Nichols | first1 = G.| last2 = Stein | first2 = C.| title = Modulation of the activity of Bcl-2 in Waldenstrom's macroglobulinemia using antisense oligonucleotides| journal = Seminars in oncology| volume = 30| issue = 2| pages = 297–299| year = 2003| pmid = 12720156| doi = 10.1053/sonc.2003.50045}}</ref>
The protein [[Src (gene)|Src tyrosine kinase]] is overexpressed in Waldenström macroglobulinemia cells compared with control B cells.<ref>{{Cite journal| last1 = Ngo | first1 = H.| last2 = Azab | first2 = A.| last3 = Farag | first3 = M.| last4 = Jia | first4 = X.| last5 = Melhem | first5 = M.| last6 = Runnels | first6 = J.| last7 = Roccaro | first7 = A.| last8 = Azab | first8 = F.| last9 = Sacco | first9 = A.| last10 = Leleu | first10 = X.| last11 = Anderson | first11 = K. C.| last12 = Ghobrial | first12 = I. M.| title = Src tyrosine kinase regulates adhesion and chemotaxis in Waldenstrom macroglobulinemia| journal = Clinical cancer research : an official journal of the American Association for Cancer Research| volume = 15| issue = 19| pages = 6035–6041| year = 2009| pmid = 19755386| pmc = 2990685| doi = 10.1158/1078-0432.CCR-09-0718}}</ref>  Inhibition of Src arrests the [[cell cycle]] at phase G<sub>1</sub> and has little effect on the survival of WM or normal cells.
[[MicroRNA]]s involved in Waldenström's:<ref>{{Cite journal| last1 = Vacca | first1 = A.| last2 = Dammacco | first2 = F.| title = MicroRNAs to know in Waldenstrom macroglobulinemia| journal = Blood| volume = 113| issue = 18| pages = 4133–4134| year = 2009| pmid = 19406998| doi = 10.1182/blood-2009-01-199828}}</ref><ref>{{Cite journal| last1 = Roccaro | first1 = A.| last2 = Sacco | first2 = A.| last3 = Chen | first3 = C.| last4 = Runnels | first4 = J.| last5 = Leleu | first5 = X.| last6 = Azab | first6 = F.| last7 = Azab | first7 = A.| last8 = Jia | first8 = X.| last9 = Ngo | first9 = H.| last10 = Melhem | first10 = M. R.| last11 = Burwick | first11 = N.| last12 = Varticovski | first12 = L.| last13 = Novina | first13 = C. D.| last14 = Rollins | first14 = B. J.| last15 = Anderson | first15 = K. C.| last16 = Ghobrial | first16 = I. M.| title = MicroRNA expression in the biology, prognosis, and therapy of Waldenström macroglobulinemia| journal = Blood| volume = 113| issue = 18| pages = 4391–4402| year = 2009| pmid = 19074725| pmc = 2943754| doi = 10.1182/blood-2008-09-178228}}</ref>
* increased expression of miRNAs-363*,<ref>http://www.mirbase.org/cgi-bin/mirna_entry.pl?acc=MI0000764</ref> -206,<ref>http://www.mirbase.org/cgi-bin/mirna_entry.pl?acc=MI0000490</ref> -494,<ref>http://www.mirbase.org/cgi-bin/mirna_entry.pl?acc=MI0003134</ref> -155,<ref>http://www.mirbase.org/cgi-bin/mirna_entry.pl?acc=MI0000681</ref> -184,<ref>http://www.mirbase.org/cgi-bin/mirna_entry.pl?acc=MI0000481</ref> -542–3p.<ref>http://www.mirbase.org/cgi-bin/mirna_entry.pl?acc=MI0003686</ref>
* decreased expression of miRNA-9*.<ref>http://www.mirbase.org/cgi-bin/mirna_entry.pl?acc=MI0000466</ref>
MicroRNA-155 regulates the proliferation and growth of WM cells in vitro and in vivo, by inhibiting MAPK/ERK, PI3/AKT, and NF-κB pathways.
In WM-cells, [[histone deacetylase]]s and histone-modifying genes are de-regulated.<ref>{{Cite journal| last1 = Roccaro | first1 = A.| last2 = Sacco | first2 = A.| last3 = Jia | first3 = X.| last4 = Azab | first4 = A.| last5 = Maiso | first5 = P.| last6 = Ngo | first6 = H.| last7 = Azab | first7 = F.| last8 = Runnels | first8 = J.| last9 = Quang | first9 = P.| last10 = Ghobrial | first10 = I. M.| title = microRNA-dependent modulation of histone acetylation in Waldenström macroglobulinemia| journal = Blood| volume = 116| issue = 9| pages = 1506–1514| year = 2010| pmid = 20519629| pmc = 2938840| doi = 10.1182/blood-2010-01-265686}}</ref>
Bone marrow tumour cells express the following antigen targets [[CD20]] (98.3%), [[CD22]] (88.3%), [[CD40]] (83.3%), [[CD52]] (77.4%), [[IgM]] (83.3%), [[MUC1]] core protein (57.8%), and 1D10 (50%).<ref>{{Cite journal| last1 = Treon | first1 = S.| last2 = Kelliher | first2 = A.| last3 = Keele | first3 = B.| last4 = Frankel | first4 = S.| last5 = Emmanouilides | first5 = C.| last6 = Kimby | first6 = E.| last7 = Schlossman | first7 = R.| last8 = Mitsiades | first8 = N.| last9 = Mitsiades | first9 = C.| last10 = Preffer | first10 = F.| last11 = Anderson | first11 = K. C.| title = Expression of serotherapy target antigens in Waldenstrom's macroglobulinemia: therapeutic applications and considerations| journal = Seminars in oncology| volume = 30| issue = 2| pages = 248–252| year = 2003| pmid = 12720146| doi = 10.1053/sonc.2003.50047}}</ref>
==Associated Conditions==
==Associated Conditions==
==Gross Pathology==
==Gross Pathology==

Revision as of 20:22, 3 November 2015

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mirdula Sharma, MBBS [2]

Overview

Pathogenesis

Waldenström's macroglobulinemia arises from B lymphocytes, which are involved in humoral immunity.

Genetics

Although believed to be a sporadic disease, studies have shown increased susceptibility within families, indicating a genetic component.[1][2] A mutation in gene MYD88 has been found to occur frequently in patients.[3] WM cells show only minimal changes in cytogenetic and gene expression profiling|gene expression studies. Their miRNA signature however differs from their normal counterpart. It is therefore believed that epigenetic modifications play a crucial role in the disease.[4]

Comparative genomic hybridization identified the following chromosomal abnormalities: deletions of 6q23 and 13q14, and gains of 3q13-q28, 6p and 18q.[5] FGFR3 is overexpressed.[6] The following signalling pathways have been implicated:

The protein Src tyrosine kinase is overexpressed in Waldenström macroglobulinemia cells compared with control B cells.[16] Inhibition of Src arrests the cell cycle at phase G1 and has little effect on the survival of WM or normal cells.

MicroRNAs involved in Waldenström's:[17][18]

MicroRNA-155 regulates the proliferation and growth of WM cells in vitro and in vivo, by inhibiting MAPK/ERK, PI3/AKT, and NF-κB pathways.

In WM-cells, histone deacetylases and histone-modifying genes are de-regulated.[26]

Bone marrow tumour cells express the following antigen targets CD20 (98.3%), CD22 (88.3%), CD40 (83.3%), CD52 (77.4%), IgM (83.3%), MUC1 core protein (57.8%), and 1D10 (50%).[27]

Associated Conditions

Gross Pathology

Micropathology

References

  1. ↑ McMaster, M. (2003). "Familial Waldenstrom's macroglobulinemia". Seminars in oncology. 30 (2): 146–152. doi:10.1053/sonc.2003.50063. PMID 12720125.
  2. ↑ McMaster, M.; Goldin, L.; Bai, Y.; Ter-Minassian, M.; Boehringer, S.; Giambarresi, T.; Vasquez, L.; Tucker, M. (2006). "Genomewide linkage screen for Waldenstrom macroglobulinemia susceptibility loci in high-risk families". American Journal of Human Genetics. 79 (4): 695–701. doi:10.1086/507687. PMC 1592553. PMID 16960805.
  3. ↑ Treon, S. P.; Xu, L.; Yang, G.; Zhou, Y.; Liu, X.; Cao, Y.; Sheehy, P.; Manning, R. J.; Patterson, C. J.; Tripsas, C.; Arcaini, L.; Pinkus, G. S.; Rodig, S. J.; Sohani, A. R.; Harris, N. L.; Laramie, J. M.; Skifter, D. A.; Lincoln, S. E.; Hunter, Z. R. (2012). "MYD88 L265P Somatic Mutation in Waldenström's Macroglobulinemia". New England Journal of Medicine. 367 (9): 826–833. doi:10.1056/NEJMoa1200710. PMID 22931316.
  4. ↑ Sacco, A.; Issa, G. C.; Zhang, Y.; Liu, Y.; Maiso, P.; Ghobrial, I. M.; Roccaro, A. M. (2010). "Epigenetic modifications as key regulators of Waldenstrom's Macroglobulinemia biology". Journal of Hematology & Oncology. 3: 38. doi:10.1186/1756-8722-3-38. PMC 2964547. PMID 20929526.
  5. ↑ Braggio, E.; Keats, J. J.; Leleu, X.; Van Wier, S. V.; Jimenez-Zepeda, V. H.; Schop, R. F. J.; Chesi, M.; Barrett, M.; Stewart, A. K.; Dogan, A.; Bergsagel, P. L.; Ghobrial, I. M.; Fonseca, R. (2009). "High-Resolution Genomic Analysis in Waldenström's Macroglobulinemia Identifies Disease-Specific and Common Abnormalities with Marginal Zone Lymphomas". Clinical Lymphoma, Myeloma & Leukemia. 9 (1): 39–42. doi:10.3816/CLM.2009.n.009. PMC 3646570. PMID 19362969.
  6. ↑ Azab, A. K.; Azab, F.; Quang, P.; Maiso, P.; Sacco, B.; Ngo, A.; Liu, H. T.; Zhang, Y.; Morgan, Y.; Roccaro, A. M.; Ghobrial, I. M. (2011). "FGFR3 is overexpressed Waldenstrom macroglobulinemia and its inhibition by Dovitinib induces apoptosis, and overcomes stroma-induced proliferation". Clinical Cancer Research. 17 (13): 4389–4399. doi:10.1158/1078-0432.CCR-10-2772. PMID 21521775.
  7. ↑ http://www.asco.org/ASCO/Abstracts+&+Virtual+Meeting/Abstracts?&vmview=abst_detail_view&confID=26&abstractID=4297
  8. ↑ Leleu, X.; Jia, X.; Runnels, J.; Ngo, H.; Moreau, A.; Farag, M.; Spencer, J.; Pitsillides, C.; Hatjiharissi, E.; Roccaro, A.; O'Sullivan, G.; McMillin, D. W.; Moreno, D.; Kiziltepe, T.; Carrasco, R.; Treon, S. P.; Hideshima, T.; Anderson, K. C.; Lin, C. P.; Ghobrial, I. M. (2007). "The Akt pathway regulates survival and homing in Waldenstrom macroglobulinemia". Blood. 110 (13): 4417–4426. doi:10.1182/blood-2007-05-092098. PMC 2234792. PMID 17761832.
  9. ↑ Mensah-Osman, E.; Al-Katib, A.; Dandashi, M.; Mohammad, R. (2003). "XK469, a topo IIbeta inhibitor, induces apoptosis in Waldenstrom's macroglobulinemia through multiple pathways". International journal of oncology. 23 (6): 1637–1644. doi:10.3892/ijo.23.6.1637. PMID 14612935.
  10. ↑ 10.0 10.1 Leleu, X.; Eeckhoute, J.; Jia, X.; Roccaro, A.; Moreau, A.; Farag, M.; Sacco, A.; Ngo, H.; Runnels, J.; Melhem, M. R.; Burwick, N.; Azab, A.; Azab, F.; Hunter, Z.; Hatjiharissi, E.; Carrasco, D. R.; Treon, S. P.; Witzig, T. E.; Hideshima, T.; Brown, M.; Anderson, K. C.; Ghobrial, I. M. (2008). "Targeting NF-kappaB in Waldenstrom macroglobulinemia". Blood. 111 (10): 5068–5077. doi:10.1182/blood-2007-09-115170. PMC 2384134. PMID 18334673.
  11. ↑ Braggio, E.; Keats, J.; Leleu, X.; Van Wier, S.; Jimenez-Zepeda, V.; Valdez, R.; Schop, R.; Price-Troska, T.; Henderson, K.; Sacco, A.; Azab, F.; Greipp, P.; Gertz, M.; Hayman, S.; Rajkumar, S. V.; Carpten, J.; Chesi, M.; Barrett, M.; Stewart, A. K.; Dogan, A.; Bergsagel, P. L.; Ghobrial, I. M.; Fonseca, R. (2009). "Identification of copy number abnormalities and inactivating mutations in two negative regulators of nuclear factor-kappaB signaling pathways in Waldenstrom's macroglobulinemia". Cancer Research. 69 (8): 3579–3588. doi:10.1158/0008-5472.CAN-08-3701. PMC 2782932. PMID 19351844.
  12. ↑ Gutiérrez, N.; Ocio, E.; De Las Rivas, J.; Maiso, P.; Delgado, M.; Fermiñán, E.; Arcos, M.; Sánchez, M.; Hernández, J.; San Miguel, J. F. (2007). "Gene expression profiling of B lymphocytes and plasma cells from Waldenström's macroglobulinemia: comparison with expression patterns of the same cell counterparts from chronic lymphocytic leukemia, multiple myeloma and normal individuals". Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 21 (3): 541–549. doi:10.1038/sj.leu.2404520. PMID 17252022.
  13. ↑ Burwick, N.; Roccaro, A.; Leleu, X.; Ghobrial, I. (2008). "Targeted therapies in Waldenström macroglobulinemia". Current opinion in investigational drugs (London, England : 2000). 9 (6): 631–637. PMID 18516762.
  14. ↑ Chng, W.; Schop, R.; Price-Troska, T.; Ghobrial, I.; Kay, N.; Jelinek, D.; Gertz, M.; Dispenzieri, A.; Lacy, M.; Kyle, R. A.; Greipp, P. R.; Tschumper, R. C.; Fonseca, R.; Bergsagel, P. L. (2006). "Gene-expression profiling of Waldenstrom macroglobulinemia reveals a phenotype more similar to chronic lymphocytic leukemia than multiple myeloma". Blood. 108 (8): 2755–2763. doi:10.1182/blood-2006-02-005488. PMC 1895596. PMID 16804116.
  15. ↑ Nichols, G.; Stein, C. (2003). "Modulation of the activity of Bcl-2 in Waldenstrom's macroglobulinemia using antisense oligonucleotides". Seminars in oncology. 30 (2): 297–299. doi:10.1053/sonc.2003.50045. PMID 12720156.
  16. ↑ Ngo, H.; Azab, A.; Farag, M.; Jia, X.; Melhem, M.; Runnels, J.; Roccaro, A.; Azab, F.; Sacco, A.; Leleu, X.; Anderson, K. C.; Ghobrial, I. M. (2009). "Src tyrosine kinase regulates adhesion and chemotaxis in Waldenstrom macroglobulinemia". Clinical cancer research : an official journal of the American Association for Cancer Research. 15 (19): 6035–6041. doi:10.1158/1078-0432.CCR-09-0718. PMC 2990685. PMID 19755386.
  17. ↑ Vacca, A.; Dammacco, F. (2009). "MicroRNAs to know in Waldenstrom macroglobulinemia". Blood. 113 (18): 4133–4134. doi:10.1182/blood-2009-01-199828. PMID 19406998.
  18. ↑ Roccaro, A.; Sacco, A.; Chen, C.; Runnels, J.; Leleu, X.; Azab, F.; Azab, A.; Jia, X.; Ngo, H.; Melhem, M. R.; Burwick, N.; Varticovski, L.; Novina, C. D.; Rollins, B. J.; Anderson, K. C.; Ghobrial, I. M. (2009). "MicroRNA expression in the biology, prognosis, and therapy of Waldenström macroglobulinemia". Blood. 113 (18): 4391–4402. doi:10.1182/blood-2008-09-178228. PMC 2943754. PMID 19074725.
  19. ↑ http://www.mirbase.org/cgi-bin/mirna_entry.pl?acc=MI0000764
  20. ↑ http://www.mirbase.org/cgi-bin/mirna_entry.pl?acc=MI0000490
  21. ↑ http://www.mirbase.org/cgi-bin/mirna_entry.pl?acc=MI0003134
  22. ↑ http://www.mirbase.org/cgi-bin/mirna_entry.pl?acc=MI0000681
  23. ↑ http://www.mirbase.org/cgi-bin/mirna_entry.pl?acc=MI0000481
  24. ↑ http://www.mirbase.org/cgi-bin/mirna_entry.pl?acc=MI0003686
  25. ↑ http://www.mirbase.org/cgi-bin/mirna_entry.pl?acc=MI0000466
  26. ↑ Roccaro, A.; Sacco, A.; Jia, X.; Azab, A.; Maiso, P.; Ngo, H.; Azab, F.; Runnels, J.; Quang, P.; Ghobrial, I. M. (2010). "microRNA-dependent modulation of histone acetylation in Waldenström macroglobulinemia". Blood. 116 (9): 1506–1514. doi:10.1182/blood-2010-01-265686. PMC 2938840. PMID 20519629.
  27. ↑ Treon, S.; Kelliher, A.; Keele, B.; Frankel, S.; Emmanouilides, C.; Kimby, E.; Schlossman, R.; Mitsiades, N.; Mitsiades, C.; Preffer, F.; Anderson, K. C. (2003). "Expression of serotherapy target antigens in Waldenstrom's macroglobulinemia: therapeutic applications and considerations". Seminars in oncology. 30 (2): 248–252. doi:10.1053/sonc.2003.50047. PMID 12720146.

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