Hematology, Endoceinology and Metabolism
Contributions
Type: Publication Only
Background
Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries but is very rare in Asian countries, including Japan. There are few reports about immunophenotypes, chromosome aberrations and mutations of immunoglobulin heavy chain gene variable region (IGVH) in Japanese CLL patients.
Aims
Hence we have conducted a nationwide registry study (CLLRSG-01) from January 2011 to clarify the characteristics of Japanese CLL patinets. We present here the interim results of prospective study.
Methods
Seventy-five untreated patients with indolent B-cell neoplasms met the inclusion criteria: (i) absolute lymphocyte counts of 5000/ul or more in the peripheral blood; or (ii) abnormal lymphocytes of 20% or more in the peripheral blood. The morphological examination was carried out according to the WHO classification by diagnostic committee. “Atypical CLL” was determined according to the morphology by the FAB classification, but this term does not mean atypical expression of surface immunophenotype. Immunophenotyping was performed using flow cytometry with a panel of antibodies including CD5, CD19, CD20, CD21, CD22, CD23, CD38, CD69, FMC7 and ZAP-70. The immunophenotypic score was calculated based on the CLL scoring system proposed by Matutes et al. We investigated del(13q14), del(11q22), del(17p13), and trisomy 12 using interphase fluorescence in situ hybridization (FISH). Cases with mantle cell lymphoma were excluded by FISH with t(11;14) probe and/or the overexpression of CCDN1 by immunostaining.
Results
According to the morphologic review of peripheral blood smear, 41 patients (55%) were classified as typical CLL, 12 (16%) as atypical CLL and 22 (29%) as other indolent B-cell tumors (others) including 8 hairy cell leukemia. The immunophenotypic profile demonstrated that the frequency of expression of CD5, CD21, CD23 and CD69 in CLL (typical and atypical) group was higher than that of others. The Matutes’ CLL scoring system showed that 27 patients (51%) with CLL had higher values (5 or 4) whereas 21 patients (95%) with others had lower score values (0-3) (p=0.004). There was no significant difference between the typical and atypical CLL in this scoring system. Of the 75 patients analyzed by FISH, 44 (59%) had at least one aberration. The most frequent abnormality was del(13q14)(37%), followed by trisomy 12 (23%), del(11q22)(7%), and del(17p13)(7%). Del(17p13) was not detected in patients with CLL, but was detected in 5 patients (23%) with others. Among CLL patients, atypical morphology was shown to correlate with ZAP-70 expression and trisomy 12 by FISH analysis in comparison with typical CLLs.
Summary
The present study demonstrated immunophenotypic and cytogenetic characteristics of CLL in Japan. Our results have shown that Japanese CLL has atypical immunophenotypes and similar chromosomal aberrations as those in Western countries. Our results should be confirmed by further Japanese and Western collaborative study.
Keyword(s): Chronic lymphocytic leukemia, FISH, Flow cytometry
Session topic: Publication Only
Type: Publication Only
Background
Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries but is very rare in Asian countries, including Japan. There are few reports about immunophenotypes, chromosome aberrations and mutations of immunoglobulin heavy chain gene variable region (IGVH) in Japanese CLL patients.
Aims
Hence we have conducted a nationwide registry study (CLLRSG-01) from January 2011 to clarify the characteristics of Japanese CLL patinets. We present here the interim results of prospective study.
Methods
Seventy-five untreated patients with indolent B-cell neoplasms met the inclusion criteria: (i) absolute lymphocyte counts of 5000/ul or more in the peripheral blood; or (ii) abnormal lymphocytes of 20% or more in the peripheral blood. The morphological examination was carried out according to the WHO classification by diagnostic committee. “Atypical CLL” was determined according to the morphology by the FAB classification, but this term does not mean atypical expression of surface immunophenotype. Immunophenotyping was performed using flow cytometry with a panel of antibodies including CD5, CD19, CD20, CD21, CD22, CD23, CD38, CD69, FMC7 and ZAP-70. The immunophenotypic score was calculated based on the CLL scoring system proposed by Matutes et al. We investigated del(13q14), del(11q22), del(17p13), and trisomy 12 using interphase fluorescence in situ hybridization (FISH). Cases with mantle cell lymphoma were excluded by FISH with t(11;14) probe and/or the overexpression of CCDN1 by immunostaining.
Results
According to the morphologic review of peripheral blood smear, 41 patients (55%) were classified as typical CLL, 12 (16%) as atypical CLL and 22 (29%) as other indolent B-cell tumors (others) including 8 hairy cell leukemia. The immunophenotypic profile demonstrated that the frequency of expression of CD5, CD21, CD23 and CD69 in CLL (typical and atypical) group was higher than that of others. The Matutes’ CLL scoring system showed that 27 patients (51%) with CLL had higher values (5 or 4) whereas 21 patients (95%) with others had lower score values (0-3) (p=0.004). There was no significant difference between the typical and atypical CLL in this scoring system. Of the 75 patients analyzed by FISH, 44 (59%) had at least one aberration. The most frequent abnormality was del(13q14)(37%), followed by trisomy 12 (23%), del(11q22)(7%), and del(17p13)(7%). Del(17p13) was not detected in patients with CLL, but was detected in 5 patients (23%) with others. Among CLL patients, atypical morphology was shown to correlate with ZAP-70 expression and trisomy 12 by FISH analysis in comparison with typical CLLs.
Summary
The present study demonstrated immunophenotypic and cytogenetic characteristics of CLL in Japan. Our results have shown that Japanese CLL has atypical immunophenotypes and similar chromosomal aberrations as those in Western countries. Our results should be confirmed by further Japanese and Western collaborative study.
Keyword(s): Chronic lymphocytic leukemia, FISH, Flow cytometry
Session topic: Publication Only