Pathology of chronic lymphocytic leukemia: an update

Inamdar, Kedar; Bueso‐Ramos, Carlos E.

doi:10.1016/j.anndiagpath.2007.08.002

Cited by 63 publications

(35 citation statements)

References 233 publications

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“…Recently, examination of lymph node CLL cells provided additional support to this hypothesis as these cells were shown to have an antiapoptotic expression profile with up-regulation of Mcl-1, Bcl-XL, and survivin and concomitant down-regulation of Noxa when compared with CLL cells in blood (17). Insights in proliferation centers in bone marrow are limited as these are almost exclusively seen in cases with extensive marrow involvement (47). We showed that in our patient cohort with stable disease, the large majority of bone marrow CLL cells did not proliferate and, in general, did not possess an altered apoptotic regulator profile compared with peripheral blood CLL cells.…”

Section: Discussionmentioning

confidence: 99%

In vivo Dynamics of Stable Chronic Lymphocytic Leukemia Inversely Correlate with Somatic Hypermutation Levels and Suggest No Major Leukemic Turnover in Bone Marrow

et al. 2008

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Although accumulating evidence indicates that chronic lymphocytic leukemia (CLL) is a disease with appreciable cell dynamics, it remains uncertain whether this also applies to patients with stable disease. In this study, 2 H 2 O was administered to a clinically homogeneous cohort of nine stable, untreated CLL patients. CLL dynamics in blood and bone marrow were determined and compared with normal B-cell dynamics in blood from five healthy individuals who underwent a similar 2 H 2 O labeling protocol. Average CLL turnover rates (0.08-0.35% of the clone per day) were f2-fold lower than average B-cell turnover rates from healthy individuals (0.34-0.89%), whereas the rate at which labeled CLL cells in blood disappeared (0.00-0.39% of B cells per day) was f10-fold lower compared with labeled B cells from healthy individuals (1.57-4.24% per day). Leukemic cell turnover variables inversely correlated with the level of somatic hypermutation of the CLL clone (IgVH mutations). Although CLL cells in bone marrow had a higher level of label enrichment than CLL cells in blood, no difference between proliferation rates and proapoptotic and antiapoptotic profiles of CLL cells from these compartments was observed. These data suggest that, in stable disease, there is a biological relationship between the degree of somatic hypermutation of the CLL clone and its dynamics in vivo. Furthermore, in contrast to lymph nodes, the bone marrow does not seem to be a major CLL proliferation site. [Cancer Res 2008;68(24):10137-44]

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Section: Discussionmentioning

confidence: 99%

In vivo Dynamics of Stable Chronic Lymphocytic Leukemia Inversely Correlate with Somatic Hypermutation Levels and Suggest No Major Leukemic Turnover in Bone Marrow

et al. 2008

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“…9 We hope with this letter to clarify for a wider audience of hematologists and pathologists that FMC7 is, in fact, an epitope of CD20.…”

Section: Fmc7 Is An Epitope Of Cd20mentioning

confidence: 99%

FMC7 is an epitope of CD20

Deans¹,

Polyak²

2008

Blood

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FMC7 is an epitope of CD20The FMC7 antibody, originally described in 1981, 1 detects an antigen expressed on mature human B cells and is used in immunophenotypic analysis and differential diagnosis of lymphomas and leukemias. The identity of the FMC7 antigen was unclear for many years. An early unconfirmed report indicated that it might be a 105 kDa protein, based on a Western blot using FMC7 and a radio-iodinated secondary antibody. 2 This finding may have deflected attention from the possibility that FMC7 was related to the 33 kDa B-cell antigen, CD20, even though the expression of FMC7 generally correlates well with that of CD20. 3,4 Serke et al provided the first evidence that FMC7 is an epitope on the CD20 molecule itself. 5 Their study showed that transient transfection of CD20 in the human K562 erythroleukemia cell line caused expression of FMC7 in approximately half of CD20-expressing cells. The data were not definitive, as weak expression and the use of a human hematopoeitic cell line allowed for the alternate interpretation that ectopically expressed CD20 may have upregulated another protein reactive with the FMC7 antibody. In 2003 we confirmed and extended their finding, demonstrating that FMC7 was very strongly and uniformly expressed on 100% of CD20-transfected non-B cells, even of nonhuman, nonhematopoietic origin. 6 Furthermore, point mutations in the extracellular region of CD20 destroyed the FMC7 epitope along with all other extracellular CD20 epitopes. 6,7 In unpublished data, we have found that deletions in the intracellular regions of CD20 also profoundly reduce FMC7 expression, presumably by affecting CD20 conformation.Importantly, the epitope is unusually sensitive to levels of membrane cholesterol. 6 FMC7 expression will be different in cells expressing the same amount of CD20 if the cholesterol level varies, as it does among cell lines and during B-cell maturation. 8 This provides an explanation for why the correlation between FMC7 and endogenous CD20 expression, while strong, is not strictly held. Cholesterol sensitivity is a common but variable feature of antibodies that detect extracellular CD20 epitopes (Figure 1). Among the 15 antibodies that we tested, FMC7 and one other antibody, CAT13.7H, fall at the extreme end of sensitivity, while rituximab and several other CD20 antibodies are far less affected.Regrettably, the description by vendors and others of FMC7 as an unidentified 105 kDa antigen persists. 9 We hope with this letter to clarify for a wider audience of hematologists and pathologists that FMC7 is, in fact, an epitope of CD20.

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“…1 It is more common in males and mostly occur after the age of 60 years. 2,3 Disease progress is quiet variable according to a number of factors.…”

Section: Introductionmentioning

confidence: 99%

Comparison of CD38, ZAP70 and hTERT Expression with Known Prognostic Markers in Patients with Chronic Lymphocytic Leukemia During Five-Year Follow- up Period

Vural¹

2014

UHOD

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Chronic Lymphocytic Leukemia (CLL) is the most common leukemia in adults. Recently CD38, ZAP70 and hTERT activity have been studied for the evaluation of the prognosis of CLL besides clinical staging and lymphocyte doubling time. There are inconsistent results regarding these markers for the evaluation of the prognosis in CLL patients. In this study CD38, ZAP70 and hTERT values in CLL patients were measured to make comparisons between each other and known prognostic factors. Thirty CLL patients who were included in the study were followed up for 5 years after the initial diagnosis. The mean hTERT value in CLL and control cases were 1.00±1.31 and 3.89±3.58, respectively (p< 0.05). The mean CD38 and ZAP70 were 6.20±7.60 and 5.51±5.67, respectively. No significant association was detected between CD38, ZAP70 and hTERT activity. There was no correlation between those parameters and known prognostic parameters such as Rai staging, peripheral lymphocyte levels, age, and sex of the patients, beta-2 microglobulin and reply to treatment in CLL. The overall five-year survival rate in CLL patients is 96.7%. The overall five-year survival rate in CLL patients is 96.7%. In conclusion, further studies including larger series of patients with longer follow-up periods are recommended.

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Pathology of chronic lymphocytic leukemia: an update

Cited by 63 publications

References 233 publications

In vivo Dynamics of Stable Chronic Lymphocytic Leukemia Inversely Correlate with Somatic Hypermutation Levels and Suggest No Major Leukemic Turnover in Bone Marrow

In vivo Dynamics of Stable Chronic Lymphocytic Leukemia Inversely Correlate with Somatic Hypermutation Levels and Suggest No Major Leukemic Turnover in Bone Marrow

FMC7 is an epitope of CD20

Comparison of CD38, ZAP70 and hTERT Expression with Known Prognostic Markers in Patients with Chronic Lymphocytic Leukemia During Five-Year Follow- up Period

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