| Objective:To analysis the clinical and biological characteristics of 1117 cases of de novo adult acute lymphoblastic leukemia in China; To explore the morphology, immunophenotype, cytogenetics, molecular genetics and clinical features of ALL patients with t(1;19)/TCF3 PBX1 or PAX5 translocations.Methods:All cases were studied by R band karyotypic analysis using direct method and/or short term culture for chromosomes preparation,?uorescence in situ hybridization (FISH) and PCR were performed to detect the TCF3 PBX1 fusion gene, FISH was used to screen out the B ALL cases had a translocation involving the PAX5 with abn(9p) abnormality, we combine all the information with morphology and clinical features to analysis the different ALL cases.Results:1 The clinical and biological characteristics of de novo acute lymphoblastic leukemia: a study based on 1117 patients in a single institution of ChinaOf the 1117 de novo ALL cases, 833 (74.6%) were classified as B ALL, 239 (23.9%) were classified as T ALL, and 45 (4%) were classified as mixed phenotype acute leukemia (MPAL). B ALLs were significantly older than T ALLs (P<0.01), the mean white blood count (WBC) and hemoglobin (Hb) were significantly lower (P<0.01). All cases were classified by France American Britain (FAB) classification, 428, 342, 35 and 267 cases were diagnosed as L1, L2, L3 and not otherwise specified (NOS), respectively. The clinical and laboratorial features were analyzed, on the respect of mean age, L1L2>NOS>L3 (74.6>70.6>52.2>14.2×109/L), the mean WBC counts of L3 cases were significantly lower than the others (P<0.001), the mean WBC counts of NOS cases were significantly lower than L1 cases (P< 0.05); on the respect of mean platelets (PLT), NOS>L3>L2>L1 (89.3>79.4>74.0>69.1×109/L), the mean PLT of NOS cases were significantly higher than L1 and L2 cases (P<0.05); on the respect of mean Hb, NOS>L3>L1>L2 (92.1>91.0>88.2>87.3g/L), the mean Hb did not vary significantly among the 4 groups (P>0.05); on the respect of mean lactate dehydrogenase (LDH), L3>L1>L2>NOS (1543.8>1047.8>1017.8>706.8U/L), the mean LDH had no significantly among the 4 groups (P>0.05).Conventional cytogenetics was performed on 1117 cases, an evaluable karyotype was obtained in 1043 cases (93.4%) and an abnormal clone was detected in 635 cases (61%). The detection rate of abnormal karyotypes in B ALL was 65.7%, 60% and 45.2% in MPAL and T ALL, respectively. A total of 256 Ph+ patients (23.5%) were detected among 1090 that were tested by conventional cytogenetics, FISH, PCR, or a combination of these methods. The incidence of Ph+ increased with patient age, but the highest frequency was observed in the 30 to 39 year old rang. Compared with Ph patients, Ph+ patients were significantly older (P<0.01), had a higher WBC (P<0.01), but had a lower LDH (P<0.01). Among 244 Ph+ patients with abnormal cytogenetics an additional aberration was observed in 155 patients (68%). The most frequent additional anomaly was gain of a Ph Chromosome. Other additional abnormalities include monosomy 7, 9p abnormalities, high hyperdiploidy, trisomy 8 and gain of chromosome X.In addition to the chromosomal abnormalities already discussed, other recurrent chromosomal abnormalities have been described in adult ALL, their frequency has been low. Other abnormalities included t(1;19)(q21;p13.3)/TCF3 PBX1 (3 patients, 3.5%), t(8;14)(q24;q32)/c MYC translocations (11 patients, 1%), 14q11 translocations (16 patients, 1.5%), 14q32 translocations (9 patients, 0.8%), del(6q) (27 patients, 2.5%), del(7p)/ 7 (13 patients, 1.2%), +8 (31 patients, 2.8%), +X (20 patients, 1.8%), abn(9p) (68 patients, 6.2%), abn(11q) (27 patients, 2.5%), del(12p) (9 patients, 0.8%), del(13q)/ 13 (15 patients, 1.4%), del(17p) (9 patients, 0.8%), complex karyotype (13 patients, 1.2%), HeH (20 patients, 1.8%), Ho Tr (9 patients, 0.8%) and Tt (9 patients, 0.8%). Any abnormal karyotype without any of the abnormalities listed earlier were classified as other abnormality, a total of 100 patients (9.2%) included in this subgroup. those with a other abnormality showed a male predominance (P<0.01), although this subgroup showed distinct age, sex, WBC, none of these features showed any signi?cant association with other Ph ALL.2 A clinical and laboratorial study of t(1;19)/TCF3 PBX1 positive adult acute lymphoblastic leukemiaOf the 1117 de novo adult ALL cases, t(1;19)(q21;p13.3)/TCF3 PBX1 was detected in 38 cases (3.5%). According to immunophenotype profiles, 36 patients with t(1;19)(q21;p13.3)/TCF3 PBX1 were classified as B ALL, the other two were classified as T ALL. 14 cases with balanced translocation of chromosome 1 and 19, der(19) t(1;19) formed from unbalanced translocation chromosome 1 and 19 in 20 patients, 3 patient's karyotype were normal, cytogenetic analysis was unsuccessful in 1 case. Distribution 34 patients with karyotypic abnormalities by hierarchical classi?cation by ploidy, 28 (82%) were observed in pseudodiploid karyotypes. 3 (9%) in hypodiploidy 45 and 3 (9%) in hyperdiploidy 47 50. 25 cases (66%) were diagnosed as L1 by FAB classification. Of the 38 patients, the median WBC counts were 20.5 (3.1~211)×109/L, median Hb was 90 (41~142) g/L, median PLT counts were 37 (12~295)×109/L,meidan LDH was 1623 (166~8293) U/L. Of the 19 inpatients, 17 cases had lymph node, spleen and/or liver infiltration, of 18 patients received chemotherapy, 17 cases(94.7%) achieved complete remission (CR), and the median relapse free survival (RFS) and median overall survival (OS) was 3.2 months and 7.2 months, respectively. Compared with other Ph patients, t(1;19)(q21;p13.3)/TCF3 PBX1 patients were significantly younger (P<0.05), had a higher LDH (P<0.05).3 The determination of the frequency and the nature of PAX5 alterations in B ALL harboring karyotypic abnormalities at chromosome 9pThe RP11 344B23 and RP11 652D9 clones which across the PAX5 gene were selected, DNA was extracted by conventional extraction method, the fluorescein labeled DNA were prepared by nicking transition. FISH was used to determinated the rearrangement or deletion of PAX5 in B ALL harboring karyotypic abnormalities at chromosome 9p. Of the 79 patients with abn(9p), the median age was 32 year old, the median WBC counts were 21.6 (1.4~382)×109/L, median Hb was 78 (31~134) g/L, median PLT counts were 47 (6~198)×109 /L,meidan LDH was 589 (75~6038) U/L. A total of 79 B ALL patients presented a abn(9p), which was observed in pseudodiploid karyotypes in 52 cases (66%) and in hypodiploidy 45 in 18 cases (23%) and in hypodiploidy 42 44 in 3 cases (4%) and in hyperdiploidy 47 in 3 cases (4%) and in near triploidy 61 72 in 2 cases (3%). Among 79 abn(9p) patients, the most frequency additional aberration was observed in 27 patients (34%) with t(9;22)(q34;q11)/BCR ABL, other additional abnormalities include t(1;19)(q21;p13.3)/TCF3 PBX1 (6 patients, 8%), a translocation involving the MLL gene (1 patient, 1%). Of the 50 cases detected by FISH, complete deletion was observed in 23 patients (46%), partial deletion was observed in 2 patients (4%), rearrangement was detected only in 1 case, the total frequency of abnormality was 52%. The karyotype of the patient with PAX5 rearrangement was 46,XY,t(2;9)(q24;p13),del(9)(p13)[7]/46,XY[3]. Of the 26 patients with PAX5 alteration, the median WBC counts were 18.6(2.8~94.6)×109/L, median Hb was 67(51~134)g/L, median PLT counts were 44(6~198)×109 /L,meidan LDH was 583(117~5658), compared with the 24 normal patients, there was no significantly association with clinical features (P>0.05).Conclusion:1 833 patients (74.6%) were classified as B ALLs, B lineage was the most frequency immunophenotype, similarly, the detection rate of abnormal karyotype in B ALL was 65.7%, B ALL was the highest frequent abnormal cytogenetics subgroup.2 The detection rate of abnormal karyotype was 61% in this series, the most frequent karyotype anomaly was t(9;22)(q34;q11.2)/BCR ABL, in addition to the Ph chromosomal abnormality, other recurrent chromosomal abnormalities have been described in adult ALL, their frequency was less than 10%.3 There were unique biological characteristics in this series, they contribute to expound the genetic characteristics of the patient population in east Asia.4 t(1;19)(q21;p13.3)/TCF3 PBX1 positive adult ALL had unique clinical and pathological features, these patiens had high remission rate but with high relapse rate and short survival time, so, they should be considered to receive intensified treatment strategies to improve outcomes.5 The detection rate of PAX5 alterations in B ALL harboring abn(9p) was 52%, the clinical features had no significantly difference between PAX5 altered and PAX5 normal patients.6 Conventional karyotype analysis is the basic genetic technology. The combination of FISH and/or PCR will provide more comprehensive genetic information.
|
PDF Full Text Request