Background: Accelerated-chronic lymphocytic leukemia (A-CLL) is a rare disease entity as it represents less than 1% of all reported cases of chronic lymphoid leukemia (CLL). Moreover, it is most likely an under diagno...Background: Accelerated-chronic lymphocytic leukemia (A-CLL) is a rare disease entity as it represents less than 1% of all reported cases of chronic lymphoid leukemia (CLL). Moreover, it is most likely an under diagnosed entity due to its rarity and the non-standardized practice of lymph node biopsy in CLL. Purpose: The aims of our work are to establish the diagnosis of A-CLL and to study the prognosis and treatment of this rare entity. Method: here, we report the clinical presentation and the follow up of two cases of A-CLL. Results: Distinguishing Richter transformation (RT) from A-CLL is important as it may result in a major change in disease management. The prognosis of A-CLL is intermediate between CLL and RT. The prognosis is mainly poor due to a predominance of poor prognostic markers including an increasing number of p53-positive cases. Conclusion: To this date, no prospective study has been led to define the best treatment for A-CLL. The shorter survival of A-CLL when compared to typical CLL implies the need of a more aggressive treatment.展开更多
Chronic lymphocytic leukemia(CLL)is common amongst leukemic malignancies,prompting dedicated investigation throughout the years.Over the last decade,the treatment for CLL has significantly advanced with agents targeti...Chronic lymphocytic leukemia(CLL)is common amongst leukemic malignancies,prompting dedicated investigation throughout the years.Over the last decade,the treatment for CLL has significantly advanced with agents targeting B-cell lymphoma 2(BCL2),Bruton's tyrosine kinase,and CD20.Single agents or combinations of these targets have proven efficacy.Unfortunately,resistance to one or multiple of the new treatment targets develops.Our review investigates various mechanisms of resistance to BCL2 inhibitors,including mutations in BCL2,alterations in the Bcl protein pathway,epigenetic modifications,genetic heterogeneity,Richter transformation,and alterations in oxidative phosphorylation.Additionally,the review will discuss potential avenues to overcome this resistance with novel agents such as bispecific antibodies,Bruton's tyrosine kinase(BTK)degraders,non-covalent BTK inhibitors,and chimeric antigen receptor T(CART).展开更多
Indolent B-cell lymphomas are a group of incurable cancers of the elderly that encompass various entities,such as chronic lymphocytic leukemia(CLL),follicular lymphoma(FL),and marginal zone lymphoma(MZL).All indolent ...Indolent B-cell lymphomas are a group of incurable cancers of the elderly that encompass various entities,such as chronic lymphocytic leukemia(CLL),follicular lymphoma(FL),and marginal zone lymphoma(MZL).All indolent lymphomas may evolve towards aggressive transformation with an increased proliferation index and decreased tumor doubling time.This transformation,which is called Richter’s syndrome in CLL,is associated with an aggressive clinical course and poor survival.At least in CLL,transformation of an indolent B-cell clone is molecularly different from that of de novo diffuse large B-cell lymphomas.1 Aging is known to be associated with immune decline,with increased inflammation,decreased immune surveillance and increased onset of malignancies among the consequences.2 Progression of indolent B-cell lymphomas is likely to be associated with escape from immune surveillance.展开更多
文摘Background: Accelerated-chronic lymphocytic leukemia (A-CLL) is a rare disease entity as it represents less than 1% of all reported cases of chronic lymphoid leukemia (CLL). Moreover, it is most likely an under diagnosed entity due to its rarity and the non-standardized practice of lymph node biopsy in CLL. Purpose: The aims of our work are to establish the diagnosis of A-CLL and to study the prognosis and treatment of this rare entity. Method: here, we report the clinical presentation and the follow up of two cases of A-CLL. Results: Distinguishing Richter transformation (RT) from A-CLL is important as it may result in a major change in disease management. The prognosis of A-CLL is intermediate between CLL and RT. The prognosis is mainly poor due to a predominance of poor prognostic markers including an increasing number of p53-positive cases. Conclusion: To this date, no prospective study has been led to define the best treatment for A-CLL. The shorter survival of A-CLL when compared to typical CLL implies the need of a more aggressive treatment.
文摘Chronic lymphocytic leukemia(CLL)is common amongst leukemic malignancies,prompting dedicated investigation throughout the years.Over the last decade,the treatment for CLL has significantly advanced with agents targeting B-cell lymphoma 2(BCL2),Bruton's tyrosine kinase,and CD20.Single agents or combinations of these targets have proven efficacy.Unfortunately,resistance to one or multiple of the new treatment targets develops.Our review investigates various mechanisms of resistance to BCL2 inhibitors,including mutations in BCL2,alterations in the Bcl protein pathway,epigenetic modifications,genetic heterogeneity,Richter transformation,and alterations in oxidative phosphorylation.Additionally,the review will discuss potential avenues to overcome this resistance with novel agents such as bispecific antibodies,Bruton's tyrosine kinase(BTK)degraders,non-covalent BTK inhibitors,and chimeric antigen receptor T(CART).
基金The group of J Feuillard is supported by grants from the Ligue Nationale contre le Cancer(Equipe Labellisee Ligue),the Institut National contre le Cancer(INCa),the Comité Orientation Recherche Cancer(CORC),the Limousin Region and the Haute Vienne and Correze comitees of the Ligue Nationale contre le Cancer and by the Lyons Club of CorrezeU Zimber-Strobl was supported by the German ResearchFoundation(SFB 1243,TP-A13).
文摘Indolent B-cell lymphomas are a group of incurable cancers of the elderly that encompass various entities,such as chronic lymphocytic leukemia(CLL),follicular lymphoma(FL),and marginal zone lymphoma(MZL).All indolent lymphomas may evolve towards aggressive transformation with an increased proliferation index and decreased tumor doubling time.This transformation,which is called Richter’s syndrome in CLL,is associated with an aggressive clinical course and poor survival.At least in CLL,transformation of an indolent B-cell clone is molecularly different from that of de novo diffuse large B-cell lymphomas.1 Aging is known to be associated with immune decline,with increased inflammation,decreased immune surveillance and increased onset of malignancies among the consequences.2 Progression of indolent B-cell lymphomas is likely to be associated with escape from immune surveillance.
