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Biomedical subjects

C H Pui

Publications and source records attributed to C H Pui.

At least 127 records · Page 7Linked to original sources
PubMed1996

Effectiveness of intensified rotational combination chemotherapy for late hematologic relapse of childhood acute lymphoblastic leukemia.

Relapsed acute lymphoblastic leukemia (ALL) usually carries a dire prognosis. We evaluated the effectiveness and long-term complications of intensive rotational combination chemotherapy for late hematologic relapse (median, 16 months after elective cessation of therapy) among 34 children and young adults (ages 4 to 23 years). Concurrent central nervous system (CNS) relapse was present in 3 cases and testicular relapse in 4. Secondary therapy comprised an intensive five-drug reinduction (6 weeks) followed by continuation treatment with four drug pairs, rotated weekly in 4-week cycles over 120 weeks. Intrathecal chemotherapy (methotrexate, hydrocortisone, cytarabine) was given three times during reinduction and every 8 weeks during continuation. Treatment was electively discontinued at week 120 in the absence of detectable disease. Thirty-three patients (97%) attained a second complete remission. At a median follow-up of 9.3 years (range, 4.5 to 11.4), estimates of 5-year second event-free and overall survival (+/- SE) are 65% +/- 8% and 79% +/- 7%, respectively. Eleven patients had a second relapse (9 marrow, 2 testicular) and one developed secondary myeloid leukemia. There have been no CNS relapses or deaths in remission. Treatment was well-tolerated and was given largely on an outpatient basis. Late effects are primarily endocrinologic; one child had a second malignant solid tumor (presumed related to initial radiation therapy) that was treated successfully. Intensive treatment with alternating non-cross-resistant drug pairs for late hematologic relapses of ALL is effective and well-tolerated, and produces results similar to those achieved in patients with newly diagnosed ALL. Event-free survival compares favorably with reports of other relapse regimens, including those incorporating bone marrow transplantation.

Adolescent↗
PubMed1996

Rearrangement of the MLL gene confers a poor prognosis in childhood acute lymphoblastic leukemia, regardless of presenting age.

MLL gene rearrangements are associated with an extremely poor prognosis in infants with acute lymphoblastic leukemia (ALL), but little is known about their clinical significance in older children. Therefore, we studied 45 cases of childhood ALL with abnormalities of chromosome 11q23 for rearrangement of the MLL gene to determine if this feature confers a uniformly poor prognosis. MLL gene rearrangements were detected in all 18 cases with the common t(4;11), t(9;11) or t(11;19) translocations, whereas only 5 of 12 patients with either unbalanced or uncommon balanced translocations demonstrated a rearrangement. Abnormalities of the MLL gene were not detected in any of the 15 cases with a deletion or inversion of the chromosomes 11q23 region. The presence of an MLL rearrangement was significantly associated with age less than 1 year (P < .001), leukocyte count >50 x 10(9)/L (P = .003), and the absence of leukemic cell CD10 expression (P < .001). In a stratified statistical analysis adjusted for age and treatment protocol, MLL gene rearrangement was correlated with an inferior treatment outcome (P = .028). The 4-year event-free survival estimate (+/- SE) was 10% +/- 6.5% for cases with a rearranged MLL gene and 64% +/- 19.2% for other cases. When infants were excluded from the analysis, MLL rearrangement was still significantly associated with a poor outcome (P = .02), and remained so with the exclusion of t(4;11)-positive cases (P = .05). Thus, regardless of presenting age, MLL gene rearrangement identifies a high-risk subgroup of patients who are not likely to be cured with conventional treatment.

Age Factors↗
PubMed1996

Stroma-supported culture in childhood B-lineage acute lymphoblastic leukemia cells predicts treatment outcome.

We developed a stroma cell culture system that suppresses apoptosis of malignant cells from cases of B-lineage acute lymphoblastic leukemia. By multiparameter flow cytometric measurements of cell recovery after culture on stromal layers, we assessed the growth potential of 70 cases of newly diagnosed B-lineage acute lymphoblastic leukemia and related the findings of treatment outcome in a single program of chemotherapy. The numbers of leukemic cells recovered after 7 d of culture ranged from < 1 to 292% (median, 91%). The basis of poor cell recoveries from stromal layers appeared to be a propensity of the lymphoblasts to undergo apoptosis. The probability of event-free survival at 4 yr of follow-up was 50 +/- 9% (SE) among patients with higher cell recoveries ( > 91%), and 94 +/- 6% among those with reduced cell recoveries (+/- 91%; P = 0.0003). The prognostic value of leukemic cell recovery after culture exceeded estimates for all other recognized high-risk features and remained the most significant after adjustment with all competing covariates. Thus, the survival ability of leukemic cells on bone marrow-derived stromal layers reflects aggressiveness of the disease and is a powerful, independent predictor of treatment outcome in children with B-lineage acute lymphoblastic leukemia.

Analysis of Variance↗
PubMed1996

Human homologue of the rat chondroitin sulfate proteoglycan, NG2, detected by monoclonal antibody 7.1, identifies childhood acute lymphoblastic leukemias with t(4;11)(q21;q23) or t(11;19)(q23;p13) and MLL gene rearrangements.

Monoclonal antibody 7.1, which recognizes the chondroitin sulfate proteoglycan molecule NG2, was used to screen prospectively blast cells from 104 consecutive children at initial presentation with acute lymphoblastic leukemia (ALL). Reactivity with this antibody was found in 9 cases (8.6%), of whom 5 had a t(4;11)(q21;q23) and 4 had a t(11;19)(p13;q23). None of the NG2- cases had either translocation. Southern blot analysis disclosed MLL gene rearrangement in only the 9 cases with 7.1 reactivity plus the t(4;11)(q21;q23) or t(11;19)(q23;p13) translocation. MLL gene rearrangements were not detected in 89 patient leukemic samples that did not express NG2, including 7 patients with del(11)(q23) or inv(11)(p13q23). As expected from the association with t(4;11) and t(11;19), NG2+ cases were significantly more likely to be infants, to have hyperleukocytosis and central nervous system involvement, to be CD10-, and to express myeloid-associated antigens CD15 and CD65. Despite short follow-up duration, 3 of the NG2+ cases have relapsed while the other 101 patients remain in remission. Thus, blast cell surface expression of NG2 is useful for identifying patients with ALL having t(4;11) or t(11;19) translocations that are associated with poor prognosis, especially in the infant age group.

Adolescent↗
PubMed1996

Clinical relevance of BCL-2 overexpression in childhood acute lymphoblastic leukemia.

Enforced BCL-2 gene expression in leukemic cell lines suppresses apoptosis and confers resistance to anticancer drugs, but the clinical significance of increased BCL-2 protein levels in acute lymphoblastic leukemia (ALL) is unknown. Among 52 children with newly diagnosed ALL, BCL-2 expression in leukemic lymphoblasts ranged widely, from 4,464 to 59,753 molecules of equivalent soluble fluorochrome per cell (MESF), as determined by flow cytometry. The mean (+/- SD) level of MESF in 43 cases of B-lineage ALL (19,410 +/- 11,834) was higher than that detected in CD10+ B-lymphoid progenitors from normal bone marrow (450 +/- 314; P < .001), and CD19+ peripheral blood B lymphocytes (7,617 +/- 1,731; P = .02). Levels of BCL-2 in T-ALL cases (17,909 +/- 18,691) were also generally higher than those found in normal CD1a+ thymocytes (1,762 +/- 670), or in peripheral blood T lymphocytes (9,687 +/- 3,019). Although higher levels of BCL-2 corresponded to higher leukemic cell recoveries after culture in serum-free medium, they did not correlate with higher cell recoveries after culture on stromal layers, or with in vitro resistance to vincristine, dexamethasone, 6-thioguanine, cytarabine, teniposide, daunorubicin or methotrexate. BCL-2 protein levels did not correlate with presenting clinical features. Unexpectedly, however, lower-than-median MESF values were significantly associated with the presence of chromosomal translocations (P = .010). Notably, all six cases with the Philadelphia chromosome, a known high-risk feature, had low levels of BCL-2 expression (P = .022). Higher levels of BCL-2 were not associated with poorer responses to therapy among 33 uniformly treated patients, and were not observed in three patients studied at relapse. In conclusion, increased BCL-2 expression in childhood ALL appears to enhance the ability of lymphoblasts to survive without essential trophic factors, and is inversely related to the presence of chromosomal translocations. However, it does not reflect increased disease aggressiveness or resistance to chemotherapy.

Adolescent↗
PubMed1996

Accumulation of methotrexate polyglutamates in lymphoblasts is a determinant of antileukemic effects in vivo. A rationale for high-dose methotrexate.

Methotrexate (MTX) is one of the most widely used drugs for the treatment of childhood acute lymphoblastic leukemia (ALL) and is commonly given in high doses. However, the rationale for high-dose MTX (HDMTX) has been challenged recently. To determine whether higher MTX polyglutamate (MTXPG) concentrations in ALL blasts translate into greater antileukemic effects, 150 children with newly diagnosed ALL were randomized to initial treatment with either HDMTX (1,000 mg/m2 intravenously over 24 h) or lower-dose MTX (30 mg/m2 by mouth every 6 h x 6). ALL blasts accumulated higher concentrations of MTXPG and long-chain MTXPG (MTXPGLC) after HDMTX (P < 0.00001). Of 101 patients evaluable for peripheral blast cytoreduction, MTXPG concentrations were higher in patients whose blast count decreased within 24 h (P = 0.005) and in those who had no detectable circulating blasts within 4 days (P = 0.004). The extent of inhibition of de novo purine synthesis in ALL blasts was significantly related to the blast concentration of MTXPGLC (IC95% = 483 pmol/10(9) blasts). The percentage of patients with 44-h MTXPGLC exceeding the IC95% was greater after HDMTX (81%) than LDMTX (46%, P < 0.0001). These data indicate that higher blast concentrations of MTXPG are associated with greater antileukemic effects, establishing a strong rationale for HD-MTX in the treatment of childhood ALL.

Adolescent↗
PubMed1996

Acute leukemia in children.

Advances in the molecular characterization of leukemic cells have greatly improved the precision of diagnosis and treatment assignment as well as the monitoring of residual disease in both acute lymphoblastic leukemia and acute myeloid leukemia. Currently, specific genetic rearrangements can be identified in as many as 50% of children with either acute lymphoblastic leukemia or acute myeloid leukemia. The genes p16 (or MTS1) and TEL/AML1 are now respectively recognized as the most common tumor suppressor and fusion genes in childhood acute lymphoblastic leukemia. Increasingly, contemporary protocols for the acute leukemias are relying on genetic information to guide treatment decisions. Examples include the use of allogeneic hematopoietic stem cell transplantation for acute lymphoblastic leukemia with the BCR-ABL fusion gene or MLL rearrangement, and for acute myeloid leukemia with monosomy 7; antimetabolite-based therapy for acute lymphoblastic leukemia cases with hyperdiploidy of more than 50 chromosomes (DNA index > or = 1.16); and retinoic acid and anthracycline-containing regimens for the acute promyelocytic acute myeloid leukemia subtype with PML-RARA fusion. Other efforts are being made to reduce the long-term sequelae of treatment. Indeed, extended intrathecal therapy and intensive systemic chemotherapy will, in all likelihood, replace cranial irradiation as subclinical central nervous system therapy for patients with intermediate-risk acute lymphoblastic leukemia, and perhaps even for those with high-risk acute lymphoblastic leukemia. The challenge now is to identify specific treatments for other genetically defined subtypes of leukemia. This goal will be realized only through protocol-based studies employing uniform criteria for defining risk status.

Acute Disease↗
PubMed1996

Uniform approach to risk classification and treatment assignment for children with acute lymphoblastic leukemia.

PURPOSE: To define more uniform criteria for risk-based treatment assignment for children with acute lymphoblastic leukemia (ALL), the Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI) sponsored a workshop in September 1993. Participants included representatives from the Childrens Cancer Group (CCG), Pediatric Oncology Group (POG), Dana-Farber Cancer Institute (DFCI), St Jude Children's Research Hospital (SJCRH), and the CTEP. METHODS: Workshop participants presented and reviewed data from ALL clinical trials, using weighted averages to combine outcome data from different groups. RESULTS: For patients with B-precursor (ie, non-T, non-B) ALL, the standard-risk category (4-year event-free survival [EFS] rate, approximately 80%) will include patients 1 to 9 years of age with a WBC count at diagnosis less than 50,000/microL. The remaining patients will be classified as having high-risk ALL (4-year EFS rate, approximately 65%). For patients with T-cell ALL, different treatment strategies have yielded different conclusions concerning the prognostic significance of T-cell immunophenotype. Therefore, some groups/institutions will classify patients with T-cell ALL as high risk, while others will assign risk for patients with T-cell ALL based on the uniform age/WBC count criteria. Workshop participants agreed that the risk category of a patient may be modified by prognostic factors in addition to age and WBC count criteria, and that a common set of prognostic factors should be uniformly obtained, including DNA index (DI), cytogenetics, early response to treatment (eg, day-14 bone marrow), immunophenotype, and CNS status. CONCLUSIONS: The more uniform approach to risk-based treatment assignment and to collection of specific prognostic factors should increase the efficiency of future ALL clinical research.

Adolescent↗
PubMed1996

Etoposide achieves potentially cytotoxic concentrations in CSF of children with acute lymphoblastic leukemia.

PURPOSE: Although epipodophyllotoxins are commonly used in contemporary treatment regimens for acute lymphoblastic leukemia (ALL), their potential role in CNS-directed therapy has received little attention. We prospectively studied 20 children during initial remission of ALL and 16 children at relapse to assess CSF penetration of etoposide. METHODS: Simultaneous plasma and CSF concentrations were assessed at a median of 2.8 hours (range, 0.4 to 5.3) after an intravenous (i.v.) or oral dose in 41 paired samples. RESULTS: Etoposide given at 300 mg/m2 i.v. to patients during first remission and at 50 or 25 mg/m2 orally to those in relapse resulted in median CSF levels of 0.175 mumol/L (range, .066 to 2.12), 0.011 mumol/L (range, .004 to .032), and 0.007 mumol/L (range, .003 to .014), respectively. The CSF etoposide concentration was > or = 10 nmol/L in 20 of 20, five of 10, and two of 11 courses following 300 mg/m2 i.v., 50 mg/m2 orally, and 25 mg/m2 orally, respectively, and was positively related to both the concurrent etoposide plasma concentration (R2 = .64) and to dose (R2 = .73). The median ratio of CSF to plasma concentration was 0.30% (range, 0.09% to 3.12%), which was not related to dose, plasma concentration, or time postdose at which samples were obtained, but was positively correlated with the CSF protein concentration (R2 = 0.43, P = .006). Both the absolute etoposide CSF concentrations (P = .008) and the ratio of CSF to plasma concentrations (P = .023) were higher among first-remission patients who had CSF leukemic blasts at diagnosis compared with those without CSF blasts. CONCLUSION: Because etoposide concentrations as low as 10 nmol/L may be cytotoxic in vitro, prolonged daily oral low-dose (50 mg/m2) or conventional i.v. doses of etoposide may contribute to successful CNS-directed therapy in children with ALL.

Administration, Oral↗
PubMed1996

Comparative cytotoxicity of dexamethasone and prednisolone in childhood acute lymphoblastic leukemia.

PURPOSE: The relative cytotoxicity of prednisolone and dexamethasone in acute lymphoblastic leukemia (ALL) is controversial. We therefore compared the direct antileukemic activities of these compounds in stroma-supported cultures of leukemic lymphoblasts. MATERIALS AND METHODS: Bone marrow samples from children with B-lineage ALL were cultured on allogeneic bone marrow-derived stromal layers and exposed to various concentrations of glucocorticoids. After 4 days of culture, the number of viable leukemic cells was counted by flow cytometry and compared with that in parallel cultures without drugs. RESULTS: In 28 B-lineage ALL samples tested, the concentration producing 50% cytotoxicity (LC50) of prednisolone ranged from 2.0 to 7,978 nmol/L (median, 43.5 nmol/L), and that of dexamethasone from 0.6 to 327 nmol/L (median, 7.5 nmol/L). Despite the wide variability of responses among samples, there was an excellent correlation between LC50 values obtained with the two drugs (linear r = .99, P < .0001; Spearman rank-order r = .77, P < .0001). The median ratio of dexamethasone to prednisolone LC50 and LC90 values was 1:5.5 (range, 1:1.0 to 1:24.4 for LC50; 1:1.1 to 1:25.5 for LC90). Studies with ALL cell lines demonstrated that both drugs were cytotoxic through induction of apoptosis. Stromal layers did not absorb or inactivate measurable amounts of corticosteroids, which indicates that the assay system did not bias results toward increased drug resistance. CONCLUSION: In a bone marrow-derived microenvironment, dexamethasone is five to six times more cytotoxic (on a molar basis) than prednisolone, in agreement with the antiinflammatory activities of these drugs. This finding may serve to guide the selection of dexamethasone dosage in the treatment of ALL.

Adolescent↗
PubMed1996

Allopurinol inhibits de novo purine synthesis in lymphoblasts of children with acute lymphoblastic leukemia.

Allopurinol is used to prevent hyperuricemia in newly diagnosed patients with acute lymphoblastic leukemia (ALL). Although allopurinol has been shown to inhibit de novo purine synthesis (DNPS) in fibroblasts in vitro, this effect has not been assessed in ALL lymphoblasts. We assessed DNPS in ALL lymphoblasts in 46 consecutive patients with ALL. DNPS was determined by 14C-formate incorporation in purine bases both at diagnosis (n = 46) and 44h after MTX therapy +/- allopurinol (n = 31). The 27 patients who had received no allopurinol prior to the diagnostic bone marrow aspirate had significantly higher rates of DNPS (median, 102 fmol new purines/nmol total purines/h) compared to the 12 patients who had received more than one dose of allopurinol (100 mg/m2 orally) (median, 2.3 fmol/nmol/h; P < 0.001); the seven patients who received one dose of allopurinol had intermediate rates of DNPS (median, 58.5 fmol/nmol/h). Among patients who were evaluable for MTX effects at 44h (n = 31), the percent inhibition of DNPS was greater in the eight patients who received concomitant allopurinol (median, 100% inhibition) compared to the 23 patients who received only methotrexate therapy (median, 89% inhibition, P = 0.03). These data indicate that allopurinol suppresses may contribute to the decrease in circulating blasts in patients with newly diagnosed acute leukemias.

Adolescent↗
PubMed1996

Heterogeneity of hyperdiploid (51-67) childhood acute lymphoblastic leukemia.

We studied the fully banded chromosomes of 182 children with hyperdiploid (51-67) acute lymphoblastic leukemia (ALL) to better delineate the heterogeneity of this disease subtype. Forty-six percent of the cases had numerical changes exclusively, while the remainder had structural as well as numerical changes. Chromosome 21 was added most often (97% of cases), followed by chromosomes 6 (86%), X (81%), 14 (80%), 4 (76%), 18 (68%), 17 (68%), 10 (56%), 8 (34%) and 5 (26%). Chromosomal translocations, including the t(1;19)(q23;p13) and t(9;22)(q34;q11), were detected in only 20% of the cases, as compared with 50% in ALL in general. The most common structural alterations were duplication of the 1q arm and isochromosome of 17q, present in 25 (14%) and nine (5%) cases, respectively. The presence of absence of structural abnormalities in these cases did not influence event-free survival, as assessed in 168 patients enrolled in three successive protocols for children with newly diagnosed ALL. By contrast, patients with 51-55 chromosomes per leukemic cell (n=105) appeared to fare worse than the 56-67 subgroup (n=63) (5-year probability of event-free survival = 72 +/- 5% (s.e.) vs 86 +/- 5%; P=0.04 by the stratified log-rank test). The poorer prognosis of the 51-55 subgroup was partly due to the higher frequency of isochromosome of 17q; 6/7 patients with the isochromosome in this group have had an adverse event. Other unfavorable features within the hyperdiploid (51-55) ALL subgroup include a low prevalence of trisomies of chromosomes 4 and 10 and a higher proportion of patients with leukocyte counts greater than 50 X 10(9)/l when compared to hyperdiploid (56-67). Thus, ALL defined by 51-55 chromosomes appears to be a clinicobiologic entity quite distinct from cases with higher modal numbers.

Adolescent↗
PubMed1996

Mutations in the gene for human dihydrofolate reductase: an unlikely cause of clinical relapse in pediatric leukemia after therapy with methotrexate.

Resistance to methotrexate (MTX) in some sublines of mammalian cells is reported to be due to one of the following amino acid substitutions in dihydrofolate reductase (DHFR) that lower inhibition by MTX: Gly15 to Trp, Leu22 to Arg or Phe or Phe31 to Trp or Ser. We have produced variants of human DHFR (hDHFR) with these substitutions by directed mutagenesis. Recombinant hDHFR variants expressed in Escherichia coli have greatly decreased inhibition by MTX, but decreased catalytic efficiency, and in one case decreased stability. When a retroviral vector encoding wild-type (wt) hDHFR or one of these variants was introduced into murine fibroblasts or bone marrow progenitors, modest protection from MTX was conferred, even by wt. Relapsed pediatric patients with acute lymphoblastic leukemia who have received multiple courses of high-dose MTX seem most likely to develop such MTX resistance. cDNA was reverse transcribed from blast mRNA from 17 of these patients. However, upon amplification and sequencing of DHFR cDNA, no resistance mutation was found. The explanation for this probably lies in the need for considerable gene amplification to offset lowered catalytic efficiency, and the need for two-base changes for most substitutions, both of which are probably infrequent events.

Adolescent↗
PubMed1996

Prognostic factors in the acute lymphoid and myeloid leukemias of infants.

The age boundaries and prognostic factors that define the infant leukemias are still controversial. We therefore analyzed event-free survival according to age group in 96 children treated for acute lymphoblastic leukemia (ALL) and 51 treated for acute myeloid leukemia (AML) before the age of 2 years. The study population was registered in consecutive institutional trials of multiagent chemotherapy conducted between 1980 and 1994. Among infants with ALL, event-free survival was significantly poorer in the 0- to 6-month-old group than in patients treated between 6 and 12 months of age (P = 0.03), whose outcome was in turn inferior to that in the 12- to 18-month and 18- to 24-month age groups (P = 0.013). Leukemic cells from ALL patients younger than 12 months had a significantly higher frequency of 11q23/MLL abnormalities, as well as better growth in stromal cell culture, compared to lymphoblasts from the older groups (P < 0.01). The only independent predictor of adverse prognosis among infants diagnosed with ALL before age 12 months was the presence of an 11q23/MLL rearrangement (P = 0.03). These findings contrast sharply with results for the AML cohort, whose event-free survival did not vary significantly by age group (P = 0.58). Male sex (P = 0.01) and leukocyte count > or = 50 x 10(9/l) (P = 0.04), but not 11q23 abnormalities, were independently associated with a poorer outcome for children with AML younger than 12 months at diagnosis. Thus, in very young children with ALL (but not AML), the rearrangement status of the 11q23/MLL region supersedes age group as a determinant of treatment outcome.

Age Factors↗
PubMed1996

High incidence of TEL/AML1 fusion resulting from a cryptic t(12;21) in childhood B-lineage acute lymphoblastic leukemia in Taiwan.

Despite its rarity by routine karyotypic analysis, cryptic t(12;21)(p12-13;q22) translocation leading to TEL/AML1 fusion has been recognized as the most frequent genetic rearrangement in childhood acute lymphoblastic leukemia (ALL) in two recent studies, one from France and the other from the United States. To estimate the frequency of this abnormality in the Chinese population, we studied 41 children with ALL and 17 with acute myeloid leukemia (AML) in two medical centers in Taiwan, using the reverse transcriptase polymerase chain reaction (RT-PCR) assay. Results of this analysis demonstrated a 17% frequency of this translocation in the ALL population overall and 19% in patients with B-lineage ALL, similar to previous findings in Caucasian children. None of the patients with AML had TEL/AML1 fusion transcripts. In addition to its association with the B-lineage immunophenotype, TEL/AML1 was also correlated with a low presenting leukocyte count and favorable age (1-10 years). These findings, combined with earlier reports, indicate that TEL/AML1 fusion is the most frequent genetic abnormality in childhood ALL, regardless of race. Molecular diagnosis of t(12;21)-positive ALL may identify a subgroup of patients who do not require intensive treatment for cure.

Adolescent↗
PubMed1996

Lack of TEL-AML1 fusion transcript resulting from a cryptic t(12;21) in adult B lineage acute lymphoblastic leukemia in Taiwan.

Cryptic t(12;21)(p12-13;q22) leading to TEL-AML1 fusion has recently been recognized as the most frequent genetic rearrangement in childhood acute lymphoblastic leukemia (ALL) in Western countries. More recently, we found a similar frequency of this abnormality in Chinese children with ALL in Taiwan. In this study, we assessed further the frequency of TEL-AML1 fusion as well as that of BCR-ABL in Chinese adults with ALL, using reverse transcriptase-polymerase chain reaction assays. Among the 81 cases with newly diagnosed B lineage ALL studied, none had the TEL-AML1 fusion whereas 30 had the BCR-ABL fusion. The lack of cases with the TEL-AML1 fusion together with the high frequency of BCR-ABL fusion could largely account for the poorer outcome of adult ALL as compared with childhood ALL.

Adolescent↗
PubMed1995

Acute lymphoblastic leukemias with deletion of 11q23 or a novel inversion (11)(p13q23) lack MLL gene rearrangements and have favorable clinical features.

Balanced translocations affecting the 11q23 region are among the most frequent chromosomal abnormalities in childhood acute lymphoblastic leukemia (ALL), comprising 5% to 6%. These cases consistently have a rearranged MLL gene and are associated with high-risk presenting features, hyperleukocytosis and younger age, and a poor treatment outcome. To assess the clinical and biologic significance of 11q23-associated structural chromosomal abnormalities other than translocations, we studied 17 cases of childhood ALL [14 with del(11)(q23) and 3 with inv(11)(p12q23)] that were identified among 785 cases with successful chromosome analysis. In contrast to reported cases with 11q23 and MLL gene rearrangement, our series was characterized by relatively low leukocyte counts (median, 15.1 x 10(9)/L), expression of CD10 antigen but not myeloid-associated CD15 and CDw65 antigens, a relatively high frequency of T-cell immunophenotypes, and a generally favorable prognosis. All 13 cases with interpretable molecular analysis lacked MLL gene rearrangements. We suggest that most cases with deletions or inversions affecting the 11q23 region represent clinically and biologically different entities as compared with those defined by 11q23 translocation.

Adolescent↗