Palabras clave
Macroglobulinemia de Waldesnström; MYD88; CXCR4; Mutaciones
Cómo citar
Stanganelli, C., Cabrera, J., & Slavutsky, I. (2021). Macroglobulinemia de Waldenström. Estudios citogenéticos y moleculares. Revista Hematología, 25(1), 21–32. Recuperado a partir de https://revistahematologia.com.ar/index.php/Revista/article/view/356
Resumen
La Macroglobulinemia de Waldenström (MW) es un linfoma linfoplasmocítico con compromiso de la médula ósea (MO) y presencia de una gammapatía monoclonal IgM. La alteración citogenética más frecuente es la deleción de parte del brazo largo del cromosoma 6 observada en el 30-54% de los casos, asociada a factores de pronóstico adverso en esta patología. Los estudios de secuenciación masiva permitieron detectar la presencia de mutaciones de los genes MYD88 y CXCR4, de valor diagnóstico y pronóstico en esta entidad. La mutación activante del gen MYD88, que determina el cambio del aminoácido leucina por prolina en la posición 265 de la proteína (MYD88L265P), se observa en el 93-97% de los pacientes con MW y en el 40-60% de los casos de gammapatía monoclonal de significado incierto (MGUS) IgM, en tanto que las mutaciones de CXCR4 se encuentran en el 30-40% de los pacientes con MW, siendo menos frecuentes en el MGUS-IgM (4-20%). CXCR4S338X es la variante más común (50% de las mutaciones); genera un codón stop que conduce a una proteína truncada en el aminoácido 338, y a la pérdida de 15 aminoácidos en el dominio C-regulador. Algunos pacientes presentan múltiples mutaciones en distintos subclones. Los casos con MYD88WT/CXCR4WHIM/WT tienen pronóstico adverso con corta sobrevida libre de progresión y global. Los pacientes con MYD88L265P/CXCR4WHIM/WT tienen buena respuesta al tratamiento, en tanto que aquellos con ambos genes mutados presentan un pronóstico intermedio. Sin duda, el análisis de estas mutaciones ha permitido profundizar la caracterización biológica de la MW haciendo factible en un futuro ampliar la posibilidad de disponer de nuevos blancos terapéuticos.
Citas
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2. Swerdlow SH, Campo E, Harris NL y col. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2008.
3. Kyle RA, Larson DR, McPhail ED y col. Fifty-year incidence of Waldenström Macroglobulinemia in Olmsted County, Minnesota, from 1961 through 2010: a population-based study with complete case capture and Hematopathologic review. Mayo Clin Proc. 2018; 93: 739-46.
4. Gertz, MA. Waldenström macroglobulinemia: 2019 update on diagnosis, risk stratification, and management. Am J Hematol. 2019; 94: 266-76.
5. Wang H, Chen Y, Li F y col. Temporal and geographic variations of Waldenström macroglobulinemia incidence: a large population-based study. Cancer 2012; 118: 3793-800.
6. Castillo JJ, Olszewski AJ, Kanan S, Meid K, Hunter ZR, Treon SP. Overall survival and competing risks of death in patients with Waldenström macroglobulinaemia: an analysis of the surveillance, epidemiology and end results database. Br J Haematol 2015; 169:81-9.
7. Sahota SS, Forconi F, Ottensmeier CH y col. Typical Waldenström macroglobulinemia is derived from a B-cell arrested after cessation of somatic mutation but prior to isotype switch events. Blood 2002; 100:1505-7.
8. Kriangkum J, Taylor BJ, Strachan E y col. Impaired class switch recombination (CSR) in Waldenström macroglobulinemia (WM) despite apparently normal CSR machinery. Blood 2006; 107: 2920-7.
9. Paiva B, Corchete LA, Vidriales MB y col. The cellular origin and malignant transformation of Waldenström macroglobulinemia. Blood 2015; 125: 2370- 80.
10. García-Sanz R, Jiménez C, Puig N y col. Origin of Waldenström's Macroglobulinaemia. Best Pract Res Clin Haematol 2016; 29: 136-47.
11. Ghobrial IM. Are you sure this is Waldenström macroglobulinemia? Hematology Am Soc Hematol Educ Program. 2012; 2012: 586-94.
12. Kristinsson SY, Bjorkholm M, Goldin LR y col. Risk of lymphoproliferative disorders among first-degree relatives of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia patients: a population-based study in Sweden. Blood 2008; 112: 3052-6.
13. Kapoor P, Paludo J, Ansell S. Waldenström Macroglobulinemia: Familial predisposition and the role of genomics in prognosis and treatment selection. Curr. Treat. Options Oncol 2016; 17: 16
14. Treon SP, Hunter ZR, Aggarwal A y col. Characterization of familial Waldenström’s macroglobulinemia. Ann Oncol 2006; 17: 488-94.
15. Steingrímsson V, Lund SH, Turesson I y col. Population-based study on the impact of the familial form of Waldenström macroglobulinemia on overall survival. Blood 2015; 125: 2174-5.
16. Dimopoulos MA, Anagnostopoulos A. Waldenström's macroglobulinemia. Best Pract Res Clin Haematol 2005; 18, 747-65.
17. Treon SP. How I treat Waldenström macroglobulinemia. Blood 2009; 114:2375-85.
18. Kapoor P, Paludo J, Vallumsetla N, Greipp PR. Waldenström macroglobulinemia: what a hematologist needs to know. Blood Rev 2015; 29:301-19.
19. Castillo JJ, Treon S. Initial evaluation of the patient with Waldenström Macroglobulinemia. Hematol Oncol Clin North Am 2018; 32: 811-20.
20. San Miguel JF, Vidriales MB, Ocio E y col. Immunophenotypic analysis of Waldenström's macroglobulinemia. Semin Oncol 2003; 30: 187-95.
21. Martín-Jiménez P, García-Sanz R, Balanzategui A y col. Molecular characterization of heavy chain immunoglobulin gene rearrangements in Waldenström’s macroglobulinemia and IgM monoclonal gammopathy of undetermined significance. Haematologica 2007; 92: 635-42.
22. Varettoni M Zibellini S, Capello D y col. Clues to pathogenesis of Waldenström macroglobulinemia and immunoglobulin M monoclonal gammopathy of undetermined significance provided by analysis of immunoglobulin heavy chain gene rearrangement and clustering of B-cell receptors. Leuk Lymphoma 2013; 54: 2485-9.
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24. Agathangelidis A, Darzentas N, Hadzidimitriou A y col. Stereotyped B-cell receptors in one-third of chronic lymphocytic leukemia: a molecular classification with implications for targeted therapies. Blood 2012; 119: 4467- 75.
25. Braggio E, Keats JJ, Leleu X y col. Identification of copy number abnormalities and inactivating mutations in two negative regulators of nuclear factor-kappaB signaling pathways in Waldenström’s macroglobulinemia. Cancer Res 2009; 69: 3579-88.
26. Braggio E, Fonseca R. Genomic abnormalities of Waldenström Macroglobulinemia and related low-grade B-cell lymphomas. Clin Lymphoma Myeloma Leuk 2013; 13: 198-201.
27. Schop RF, Jalal SM, Van Wier SA y col. Deletions of 17p13.1 and 13q14 are uncommon in Waldenström macroglobulinemia clonal cells and mostly seen at the time of disease progression. Cancer Genet Cytogenet 2002; 132: 55-60.
28. Rivera A, Li M, Beltran G, Krause J. Trisomy 4 as the sole cytogenetic abnormality in a Waldenström macroglobulinemia. Cancer Genet Cytogenet 2002; 133: 172–3.
29. Terre C, Nguyen-Khac F, Barin C y col. Trisomy 4, a new chromosomal abnormality in Waldenström's macroglobulinemia: a study of 39 cases. Leukemia 2006; 20: 1634-6.
30. Braggio E, Dogan A, Keats JJ y col. Genomic analysis of marginal zone and lymphoplasmacytic lymphomas identified common and disease-specific abnormalities. Mod Pathol 2012; 25: 651-60.
31. Nguyen-Khac F, Lambert J, Chapiro E y col. Chromosomal aberrations and their prognostic value in a series of 174 untreated patients with Waldenström’s macroglobulinemia. Haematologica 2013; 98: 649-54.
32. Schop R, Kuehl W, Van Wier S y col. Waldenström macroglobulinemia neoplastic cells lack immunoglobulin heavy chain locus translocations but have frequent 6q deletions. Blood 2002; 100: 2996–3001.
33. Ocio EM, Schop RF, Gonzalez B, y col. 6q deletion in Waldenström macroglobulinemia is associated with features of adverse prognosis. Br J Haematol.2007; 136: 80- 6.
34. Chang H, Qi C, Trieu Y y col. Prognostic relevance of 6q deletion in Waldenström's macroglobulinemia: a multicenter study. Clin Lymphoma Myeloma Leuk 2009; 9: 36-8.
35. Hunter ZR, Xu L, Yang G y col. The genomic landscape of Waldenstöm’s Macroglobulinemia is characterized by highly recurring MYD88 and WHIM- like CXCR4 mutations, and small somatic deletions associated with B-cell lymphomagenesis. Blood 2014; 123: 1637-46.
36. Varettoni M, Zibellini S, Defrancesco I y col. Pattern of somatic mutations in patients with Waldenström macroglobulinemia or IgM monoclonal gammopathy of undetermined significance. Haematologica 2017; 102: 2077- 85.
37. Guerrera ML, Tsakmaklis N, Xu Ly col. MYD88 mutated and wild-type Waldenström’s Macroglobulinemia: Characterization of chromosome 6q gene losses and their mutual exclusivity with mutations in CXCR4. Haematologica 2018; 103: e408-e11.
38. Sekiguchi N, Nomoto J, Nagata A y col. Gene expression profile signature of aggressive Waldenström Macroglobulinemia with chromosome 6q deletion. Biomed Res Int 2018; 2018: 6728128.
39. Shaffer AL, Lin KI, Kuo TC y col. Blimp-1 orchestrates plasma cell differentiation by extinguishing the mature B cell gene expression program. Immunity 2002; 17: 51-62.
40. Hodge LS, Ziesmer SC, Yang ZZ y col. IL-21 in the bone marrow microenvironment contributes to IgM secretion and proliferation of malignant cells in Waldenström macroglobulinemia. Blood 2012; 120: 3774-82.
41. Treon SP, Xu L, Yang G, Zhou Y y col. MYD88 L265P somatic mutation in Waldenström's macroglobulinemia. N Engl J Med 2012; 367: 826-33.
42. Xu L, Hunter ZR, Tsakmaklis N y col: Clonal architecture of CXCR4 WHIM- like mutations in Waldenström macroglobulinaemia. Br J Haematol 2016; 172:735-44.
43. Castillo JJ, Hunter ZR, Yang G, Treon SP. Novel Approaches to targeting MYD88 in Waldenström Macroglobulinemia. Expert Rev Hematol 2017; 10: 739-44
44. Treon S, Cao Y, Xu L y col. Somatic mutations in MYD88 and CXCR4 are determinants of clinical presentation and overall survival in Waldenström macroglobulinemia. Blood 2014; 123: 2791-6.
45. Poulain S, Roumier C, Decambron A y col: MYD88 L265P mutation in Waldenström macroglobulinemia. Blood 2013; 121: 4504-11.
46. Treon SP, Gustine J, Xu L y col: MYD88 wild-type Waldenström macroglobulinaemia: Differential diagnosis, risk of histological transformation, and overall survival. Br J Haematol 2018; 180: 374-80.
47. Xu L, Hunter Z, Guang Y y col. MYD88 L265P in Waldenström macroglobulinemia, immunoglobulin M monoclonal gammopathy, and other B-cell lymphoproliferative disorders using conventional and quantitative allele-specific polymerase chain reaction. Blood 2013; 121: 2051-8.
48. Capaldi I, May A, Schmitt-Graeff A y col. Detection of MYD88 L265P mutations in formalin-fixed and decalcified BM biopsies from patients with lymphoplasmacytic lymphoma. Exp Mol Pathol 2014; 97: 57-65.
49. Xu L, Hunter ZR, Yang G y col. Detection of MYD88 L265P in peripheral blood of patients with Waldenström’s macroglobulinemia and IgM monoclonal gammopathy of undetermined significance. Leukemia 2014; 28: 1698-704.
50. Gustine J, Meid K, Xu L, Hunter ZR, Castillo JJ, Treon SP. To select or not to select? The role of B- cell selection in determining the MYD88 mutation status in Waldenström macroglobulinaemia. Br J Haematol 2017; 176: 822-4.
51. Drandi D, Genuardi E, Dogliotti I y col. Highly sensitive MYD88L265P mutation detection by droplet digital polymerase chain reaction in Waldenström macroglobulinemia. Haematologica 2018; 103: 1029-37.
52. Greco A, Tedeschi A, Varettoni M y col.Factors predicting transformation of asymptomatic IgM monoclonal gammopathy. Clin. Lymphoma Myeloma Leuk 2011; 11, 77-9.
53. Varettoni M, Arcaini L, Zibellini S y col. Prevalence and clinical significance of the MYD88 (L265P) somatic mutation in Waldenström's macroglobulinemia and related lymphoid neoplasms. Blood 2013; 121, 2522-8.
54. Kyle RA, Benson JT, Larson DR y col. Progression in smoldering Waldenström macroglobulinemia: long-term results. Blood 2012; 119: 4462- 6.
55. Yang G, Zhou Y, Liu X y col. A mutation in MYD88 (L265P) supports the survival of lymphoplasmacytic cells by activation of Bruton tyrosine kinase in Waldenström macroglobulinemia. Blood 2013; 122: 1222-32.
56. Roccaro AM, Sacco A, Jimenez C y col. C1013G/CXCR4 acts as a driver mutation of tumor progression and modulator of drug resistance in lymphoplasmacytic lymphoma. Blood 2014; 123: 4120-31.
57. Hunter ZR, Yang G, Xu L y col. Genomics, signaling, and treatment of Waldenström macroglobulinemia. J Clin Oncol 2017; 35: 994-1001.
58. Dotta L, Tassone L, Badolato R. Clinical and genetic features of warts, hypogammaglobulinemia, infections and myelokathexis (WHIM) syndrome. Current Mol Med 2011; 11, 317-25.
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2. Swerdlow SH, Campo E, Harris NL y col. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2008.
3. Kyle RA, Larson DR, McPhail ED y col. Fifty-year incidence of Waldenström Macroglobulinemia in Olmsted County, Minnesota, from 1961 through 2010: a population-based study with complete case capture and Hematopathologic review. Mayo Clin Proc. 2018; 93: 739-46.
4. Gertz, MA. Waldenström macroglobulinemia: 2019 update on diagnosis, risk stratification, and management. Am J Hematol. 2019; 94: 266-76.
5. Wang H, Chen Y, Li F y col. Temporal and geographic variations of Waldenström macroglobulinemia incidence: a large population-based study. Cancer 2012; 118: 3793-800.
6. Castillo JJ, Olszewski AJ, Kanan S, Meid K, Hunter ZR, Treon SP. Overall survival and competing risks of death in patients with Waldenström macroglobulinaemia: an analysis of the surveillance, epidemiology and end results database. Br J Haematol 2015; 169:81-9.
7. Sahota SS, Forconi F, Ottensmeier CH y col. Typical Waldenström macroglobulinemia is derived from a B-cell arrested after cessation of somatic mutation but prior to isotype switch events. Blood 2002; 100:1505-7.
8. Kriangkum J, Taylor BJ, Strachan E y col. Impaired class switch recombination (CSR) in Waldenström macroglobulinemia (WM) despite apparently normal CSR machinery. Blood 2006; 107: 2920-7.
9. Paiva B, Corchete LA, Vidriales MB y col. The cellular origin and malignant transformation of Waldenström macroglobulinemia. Blood 2015; 125: 2370- 80.
10. García-Sanz R, Jiménez C, Puig N y col. Origin of Waldenström's Macroglobulinaemia. Best Pract Res Clin Haematol 2016; 29: 136-47.
11. Ghobrial IM. Are you sure this is Waldenström macroglobulinemia? Hematology Am Soc Hematol Educ Program. 2012; 2012: 586-94.
12. Kristinsson SY, Bjorkholm M, Goldin LR y col. Risk of lymphoproliferative disorders among first-degree relatives of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia patients: a population-based study in Sweden. Blood 2008; 112: 3052-6.
13. Kapoor P, Paludo J, Ansell S. Waldenström Macroglobulinemia: Familial predisposition and the role of genomics in prognosis and treatment selection. Curr. Treat. Options Oncol 2016; 17: 16
14. Treon SP, Hunter ZR, Aggarwal A y col. Characterization of familial Waldenström’s macroglobulinemia. Ann Oncol 2006; 17: 488-94.
15. Steingrímsson V, Lund SH, Turesson I y col. Population-based study on the impact of the familial form of Waldenström macroglobulinemia on overall survival. Blood 2015; 125: 2174-5.
16. Dimopoulos MA, Anagnostopoulos A. Waldenström's macroglobulinemia. Best Pract Res Clin Haematol 2005; 18, 747-65.
17. Treon SP. How I treat Waldenström macroglobulinemia. Blood 2009; 114:2375-85.
18. Kapoor P, Paludo J, Vallumsetla N, Greipp PR. Waldenström macroglobulinemia: what a hematologist needs to know. Blood Rev 2015; 29:301-19.
19. Castillo JJ, Treon S. Initial evaluation of the patient with Waldenström Macroglobulinemia. Hematol Oncol Clin North Am 2018; 32: 811-20.
20. San Miguel JF, Vidriales MB, Ocio E y col. Immunophenotypic analysis of Waldenström's macroglobulinemia. Semin Oncol 2003; 30: 187-95.
21. Martín-Jiménez P, García-Sanz R, Balanzategui A y col. Molecular characterization of heavy chain immunoglobulin gene rearrangements in Waldenström’s macroglobulinemia and IgM monoclonal gammopathy of undetermined significance. Haematologica 2007; 92: 635-42.
22. Varettoni M Zibellini S, Capello D y col. Clues to pathogenesis of Waldenström macroglobulinemia and immunoglobulin M monoclonal gammopathy of undetermined significance provided by analysis of immunoglobulin heavy chain gene rearrangement and clustering of B-cell receptors. Leuk Lymphoma 2013; 54: 2485-9.
23. Gachard N, Parrens M, Soubeyran I y col. IGHV gene features and MYD88 L265P mutation separate the three marginal zone lymphoma entities and Waldenström macroglobulinemia/lymphoplasmacytic lymphomas. Leukemia 2013; 27: 183-9.
24. Agathangelidis A, Darzentas N, Hadzidimitriou A y col. Stereotyped B-cell receptors in one-third of chronic lymphocytic leukemia: a molecular classification with implications for targeted therapies. Blood 2012; 119: 4467- 75.
25. Braggio E, Keats JJ, Leleu X y col. Identification of copy number abnormalities and inactivating mutations in two negative regulators of nuclear factor-kappaB signaling pathways in Waldenström’s macroglobulinemia. Cancer Res 2009; 69: 3579-88.
26. Braggio E, Fonseca R. Genomic abnormalities of Waldenström Macroglobulinemia and related low-grade B-cell lymphomas. Clin Lymphoma Myeloma Leuk 2013; 13: 198-201.
27. Schop RF, Jalal SM, Van Wier SA y col. Deletions of 17p13.1 and 13q14 are uncommon in Waldenström macroglobulinemia clonal cells and mostly seen at the time of disease progression. Cancer Genet Cytogenet 2002; 132: 55-60.
28. Rivera A, Li M, Beltran G, Krause J. Trisomy 4 as the sole cytogenetic abnormality in a Waldenström macroglobulinemia. Cancer Genet Cytogenet 2002; 133: 172–3.
29. Terre C, Nguyen-Khac F, Barin C y col. Trisomy 4, a new chromosomal abnormality in Waldenström's macroglobulinemia: a study of 39 cases. Leukemia 2006; 20: 1634-6.
30. Braggio E, Dogan A, Keats JJ y col. Genomic analysis of marginal zone and lymphoplasmacytic lymphomas identified common and disease-specific abnormalities. Mod Pathol 2012; 25: 651-60.
31. Nguyen-Khac F, Lambert J, Chapiro E y col. Chromosomal aberrations and their prognostic value in a series of 174 untreated patients with Waldenström’s macroglobulinemia. Haematologica 2013; 98: 649-54.
32. Schop R, Kuehl W, Van Wier S y col. Waldenström macroglobulinemia neoplastic cells lack immunoglobulin heavy chain locus translocations but have frequent 6q deletions. Blood 2002; 100: 2996–3001.
33. Ocio EM, Schop RF, Gonzalez B, y col. 6q deletion in Waldenström macroglobulinemia is associated with features of adverse prognosis. Br J Haematol.2007; 136: 80- 6.
34. Chang H, Qi C, Trieu Y y col. Prognostic relevance of 6q deletion in Waldenström's macroglobulinemia: a multicenter study. Clin Lymphoma Myeloma Leuk 2009; 9: 36-8.
35. Hunter ZR, Xu L, Yang G y col. The genomic landscape of Waldenstöm’s Macroglobulinemia is characterized by highly recurring MYD88 and WHIM- like CXCR4 mutations, and small somatic deletions associated with B-cell lymphomagenesis. Blood 2014; 123: 1637-46.
36. Varettoni M, Zibellini S, Defrancesco I y col. Pattern of somatic mutations in patients with Waldenström macroglobulinemia or IgM monoclonal gammopathy of undetermined significance. Haematologica 2017; 102: 2077- 85.
37. Guerrera ML, Tsakmaklis N, Xu Ly col. MYD88 mutated and wild-type Waldenström’s Macroglobulinemia: Characterization of chromosome 6q gene losses and their mutual exclusivity with mutations in CXCR4. Haematologica 2018; 103: e408-e11.
38. Sekiguchi N, Nomoto J, Nagata A y col. Gene expression profile signature of aggressive Waldenström Macroglobulinemia with chromosome 6q deletion. Biomed Res Int 2018; 2018: 6728128.
39. Shaffer AL, Lin KI, Kuo TC y col. Blimp-1 orchestrates plasma cell differentiation by extinguishing the mature B cell gene expression program. Immunity 2002; 17: 51-62.
40. Hodge LS, Ziesmer SC, Yang ZZ y col. IL-21 in the bone marrow microenvironment contributes to IgM secretion and proliferation of malignant cells in Waldenström macroglobulinemia. Blood 2012; 120: 3774-82.
41. Treon SP, Xu L, Yang G, Zhou Y y col. MYD88 L265P somatic mutation in Waldenström's macroglobulinemia. N Engl J Med 2012; 367: 826-33.
42. Xu L, Hunter ZR, Tsakmaklis N y col: Clonal architecture of CXCR4 WHIM- like mutations in Waldenström macroglobulinaemia. Br J Haematol 2016; 172:735-44.
43. Castillo JJ, Hunter ZR, Yang G, Treon SP. Novel Approaches to targeting MYD88 in Waldenström Macroglobulinemia. Expert Rev Hematol 2017; 10: 739-44
44. Treon S, Cao Y, Xu L y col. Somatic mutations in MYD88 and CXCR4 are determinants of clinical presentation and overall survival in Waldenström macroglobulinemia. Blood 2014; 123: 2791-6.
45. Poulain S, Roumier C, Decambron A y col: MYD88 L265P mutation in Waldenström macroglobulinemia. Blood 2013; 121: 4504-11.
46. Treon SP, Gustine J, Xu L y col: MYD88 wild-type Waldenström macroglobulinaemia: Differential diagnosis, risk of histological transformation, and overall survival. Br J Haematol 2018; 180: 374-80.
47. Xu L, Hunter Z, Guang Y y col. MYD88 L265P in Waldenström macroglobulinemia, immunoglobulin M monoclonal gammopathy, and other B-cell lymphoproliferative disorders using conventional and quantitative allele-specific polymerase chain reaction. Blood 2013; 121: 2051-8.
48. Capaldi I, May A, Schmitt-Graeff A y col. Detection of MYD88 L265P mutations in formalin-fixed and decalcified BM biopsies from patients with lymphoplasmacytic lymphoma. Exp Mol Pathol 2014; 97: 57-65.
49. Xu L, Hunter ZR, Yang G y col. Detection of MYD88 L265P in peripheral blood of patients with Waldenström’s macroglobulinemia and IgM monoclonal gammopathy of undetermined significance. Leukemia 2014; 28: 1698-704.
50. Gustine J, Meid K, Xu L, Hunter ZR, Castillo JJ, Treon SP. To select or not to select? The role of B- cell selection in determining the MYD88 mutation status in Waldenström macroglobulinaemia. Br J Haematol 2017; 176: 822-4.
51. Drandi D, Genuardi E, Dogliotti I y col. Highly sensitive MYD88L265P mutation detection by droplet digital polymerase chain reaction in Waldenström macroglobulinemia. Haematologica 2018; 103: 1029-37.
52. Greco A, Tedeschi A, Varettoni M y col.Factors predicting transformation of asymptomatic IgM monoclonal gammopathy. Clin. Lymphoma Myeloma Leuk 2011; 11, 77-9.
53. Varettoni M, Arcaini L, Zibellini S y col. Prevalence and clinical significance of the MYD88 (L265P) somatic mutation in Waldenström's macroglobulinemia and related lymphoid neoplasms. Blood 2013; 121, 2522-8.
54. Kyle RA, Benson JT, Larson DR y col. Progression in smoldering Waldenström macroglobulinemia: long-term results. Blood 2012; 119: 4462- 6.
55. Yang G, Zhou Y, Liu X y col. A mutation in MYD88 (L265P) supports the survival of lymphoplasmacytic cells by activation of Bruton tyrosine kinase in Waldenström macroglobulinemia. Blood 2013; 122: 1222-32.
56. Roccaro AM, Sacco A, Jimenez C y col. C1013G/CXCR4 acts as a driver mutation of tumor progression and modulator of drug resistance in lymphoplasmacytic lymphoma. Blood 2014; 123: 4120-31.
57. Hunter ZR, Yang G, Xu L y col. Genomics, signaling, and treatment of Waldenström macroglobulinemia. J Clin Oncol 2017; 35: 994-1001.
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