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At least 19 recordsLinked to original sources
PubMed1990

Significance of lineage specific differentiation markers for complex classification of acute leukemias. II. Acute lymphoblastic leukemias.

Acute lymphoblastic leukemias originate from cells committed either to the T-lineage (T-ALL) or B-lineage (nonT-ALL). Leukemic cells are allocated to these lineages according to the expression of lineage specific differentiation markers (LSDM), which are T-cell antigen receptors for the T-cell lineage and immunoglobulins for the B-cell lineage. T-ALL seem to be one type of disease, among nonT-ALL it is possible to distinguish several types of diseases according to the immunoglobulin expression and clinical findings. The specificity of monoclonal antibodies and other markers is discussed with regard to the classification of ALL and "hybrid acute leukemias" (hAL), the latter with cells differentiating into myeloid and lymphoid lineages. The existence of a single hAL has not yet been reliably proved with the use of LSDM. Short-term cultures of leukemic cells represent useful diagnostic tools particularly for acute unclassifiable leukemias. Present knowledge of karyotype findings in acute leukemias classified according to LSDM is reviewed and the necessity to introduce a complex classification on this basis stressed.

Cell Differentiation↗
PubMed1988

Childhood acute lymphoblastic leukemia.

Acute lymphoblastic leukemia accounts for 80% of leukemia in children. The exact cause is unknown, but some genetic, immunologic, viral, and environmental factors have been implicated. Symptoms at the time of diagnosis frequently include fever, bleeding, fatigue, and irritability. Initial white blood cell count and patient age at diagnosis are the most reliable indicators of prognosis. Acute lymphoblastic leukemia is a heterogenous disease. Lymphoblast morphology, immunologic markers, enzyme abnormalities, cytogenetic findings, and staining characteristics in conjunction with clinical characteristics allow classification into risk groups. Appropriate therapy for each risk group is based on these parameters. Combination chemotherapy administered alone or with additional chemotherapy or radiotherapy to sanctuary sites is the principal modality for treatment of ALL. Optimal therapy for relapse has not yet been determined, but for patients with appropriate donors, allogeneic bone marrow transplant is promising. Common complications of chemotherapy include tumor lysis syndrome, myelosuppression, and other problems such as gastrointestinal toxicity, neurotoxicity and cardiac toxicity. Significant late effects of chemotherapy include neurological impairment ranging from learning problems to leukoencephalopathy and a possible increased risk of second malignancy. Complete remission is achieved in 95% of children with acute lymphoblastic leukemia, and more than 55% will continue to be in complete remission at five years. Optimal CNS prophylaxis, effective treatment of relapse, and adjustment of therapy to minimize acute and late adverse effects are a continuing challenge. With improved understanding of biologic factors, and development of more specific therapy for each subgroup, children with acute lymphoblastic leukemia should enjoy a better long term outcome.

Adolescent↗
PubMed2003

Progress and challenges in the therapy of adult acute lymphoblastic leukemia.

Acute lymphoblastic leukemia is a heterogeneous disease with distinct biologic and prognostic groupings. Although current therapies result in high complete remission rates, long-term disease-free survival rates have remained disappointingly low. Results from recent studies using risk-tailored approaches suggest improvement in overall survival for high-risk groups, such as those with Philadelphia chromosome-positive acute lymphoblastic leukemia. Furthermore, the incorporation of imatinib mesylate into the treatment regimen for Philadelphia chromosome-positive acute lymphoblastic leukemia patients may lead to better outcomes. Finally, quantification of minimal residual disease at various time points during therapy is being investigated as a means to predict more accurately a patient's response to therapy, and to make therapeutic decisions.

Adult↗
PubMed1999

Investigation of clonal involvement of myeloid cells in Philadelphia-positive and high hyperdiploid acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) with a high hyperdiploid clone has a good prognosis for both childhood and adult patients while patients with Philadelphia-positive (Ph) ALL do badly at all age groups. It has been suggested that different responses to treatment might be related to the cell of origin of the leukemia with 'stem cell' cases responding less well than those arising in a lymphoid committed progenitor cell. The clonal involvement of different cell lineages in 12 patients with acute lymphoblastic leukemia has been examined by applying fluorescence in situ hybridization (FISH) to detect chromosomal abnormalities in bone marrow cells previously identified by morphology and/or immunology. The karyotype of the malignant clone was either high hyperdiploid or Philadelphia translocation (Ph) positive with a breakpoint in the minor breakpoint cluster region of the BCRgene (m-BCR) or in the major breakpoint cluster region of the BCR gene (M-BCR). The high hyperdiploid clone, in each case, was found in cells of the B-lymphoid (CD19+) lineage but not in T cells (CD3+) or in cells of the myeloid (CD13+) or erythroid (glycophorin A+) lineages, indicative of a lymphoid committed progenitor cell. Heterogeneity of lineage involvement was found in Ph+ ALL: the m-BCR Ph+ clone was found in lymphoid/blast cells but not in neutrophils or eosinophils. In contrast both M-BCR Ph+ clones were detected in myeloid as well as lymphoid lineages, indicative of a stem cell origin.

Adolescent↗
PubMed1981

Ovarian tumor as manifestation of relapse in acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) was initially diagnosed in a 12-year-old girl. Maintenance chemotherapy was discontinued after 32 months of continuous remission. Relapse of ALL occurred ten months after cessation of chemotherapy. Twenty-one months after relapse, she presented with a large ovarian tumor due to leukemic infiltration while her bone marrow and central nervous system (CNS) were still in remission. She remained in bone marrow and CNS remission when disseminated leukemic infiltration of the peritoneum was found seven months later. She died of bone marrow relapse 11 months after ovarian relapse, six years and two months after the initial diagnosis. In contrast to testicular relapse, ovarian relapses in acute lymphoblastic leukemia are rarely reported.

Child↗
PubMedDate not supplied

Back pain and vertebral compression: an uncommon presentation of childhood acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) presenting with bone pain and leukopenia is a recognized clinicopathological complex. Three patients with ALL presented with back pain as the major symptom. These cases, together with those previously described in the literature, illustrate that delay in diagnosis frequently occurs, with the classic features of the disease being uniformly absent. The reasons for the etiology of the bone pain in ALL are in dispute. It would appear, however, that if early diagnosis can be made, then prognosis is not impaired.

Acute Disease↗
PubMed2004

Genetic polymorphisms and susceptibility to childhood acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most common form of pediatric cancer. Although exposure to environmental agents appears to predispose individuals to this disease, little attention has been paid to the role of genetic susceptibility to environmental exposures in the etiology of childhood ALL. The enzymes GSTM1, GSTT1, GSTP1, CYP1A1, and CYP2E1 are involved in the bioactivation and detoxification of a variety of xenobiotics present in food, organic solvents, tobacco smoke, drugs, alcoholic drinks, pesticides, and environmental pollutants. Polymorphisms in the genes coding for these enzymes have been associated with increased susceptibility to different cancers, including hematologic malignancies. To investigate whether these polymorphisms represent risk-modifying factors for childhood ALL, a study was conducted involving 113 Brazilian patients of childhood ALL and 221 controls with similar ethnic backgrounds. The data revealed that carriers of the rare GSTP1 Val allele were at higher risk of ALL (odds ratio [OR] = 2.7; 95% confidence interval [CI] = 1.1-6.8; P = 0.04). No difference was found in the prevalence of the GSTM1 and GSTT1 null genotypes between ALL patients and the controls, and no association was found between CYP1A1*2 and CYP2E1*3 variants and ALL. However, when the mutant CYP1A1 and CYP2E1 alleles were considered together with the GSTM1 and GSTP1 risk-elevating genotypes, the risk of ALL was increased further (OR = 10.3; 95% CI = 1.0-111.8; P = 0.05), suggesting a combined effect. These results imply that genetic variants of xenobiotic metabolizing genes influence the risk of developing childhood ALL.

Adolescent↗
PubMed1992

Hyperdiploidy arising from near-haploidy in childhood acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) of childhood is frequently characterized by a hyperdiploid karyotype. Typically, most of the affected chromosomes in the abnormal clone are present in three copies. We have studied two patients with hyperdiploid ALL whose leukemic cells were atypical in that all or most of the chromosomes were present in either two or four copies, raising a suspicion that the observed karyotype arose through duplication of chromosomes in a precursor cell with a near-haploid chromosome number. Analysis of restriction fragment length polymorphisms confirmed that both cases arose from a near-haploid cell; all informative disomic chromosomes tested had loss of heterozygosity. Furthermore, the hyperdiploid karyotypes did not arise via a perfect haploid cell with exactly 23 chromosomes, because tetrasomic chromosomes remained heterozygous. These two patients probably are classified best as near-haploid cases, which often are observed to have a co-existing hyperdiploid clone with a duplicated chromosome set. The distinction between typical hyperdiploidy and hyperdiploidy arising via a near-haploid cell may be clinically important, because the prognosis for patients with a hyperdiploid karyotype is favorable in comparison to that of patients with a near-haploid karyotype.

Adolescent↗
PubMed2002

Role of NQO1, MPO and CYP2E1 genetic polymorphisms in the susceptibility to childhood acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. The genetic factors underlying the susceptibility to this disease remain elusive. The enzymes CYP2E1, MPO and NQO1 are involved in the biotransformation of a variety of xenobiotics present in organic solvents, tobacco smoke, drugs, plastic derivatives and pesticides. They also control the level of the oxidative stress by catalyzing the formation of free radicals or by protecting cells from their deleterious effect. DNA variants in the corresponding genes have been associated with an increased susceptibility to different adult cancers, including hematologic malignancies. To investigate whether they represent risk-modifying factors in childhood ALL, we conducted a case-control study involving 174 patients and 337 controls, both of French-Canadian origin. We found that carriers of the CYP2E1*5 variant were at 2.8-fold higher risk of ALL (95%CI, 1.2-6.4) and that NQO1 alleles *2 and *3 contributed to the risk of ALL as well (OR = 1.7, 95%CI, 1.2-2.4). No such association was found with MPO alone. However, when the wild-type MPO allele was considered together with the CYP2E1 and NQO1 risk-elevating genotypes, the risk of ALL was increased further (OR = 5.4, 95%CI, 1.2-23.4) suggesting a combined effect. We also found a gene-gene interaction between the GSTM1 null genotype and NQO1 mutant alleles. It is therefore plausible that exposure to xenobiotics metabolized by these enzymes play a role in the etiology of childhood ALL.

Case-Control Studies↗
PubMed2004

Bone relapse in acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) can occasionally relapse in unusual extramedullary sites like bone. Here we present a 6.5-year old boy with 'T' cell ALL who developed a swelling in left tibia which was infiltrated with lymphoblasts 7 months after completion of chemotherapy. Bone marrow and cerebrospinal fluid were negative for blasts. This is the first reported case of bone relapse in ALL from India. We discuss the previous cases of isolated bone relapse in ALL reported in English literature.

Bone and Bones↗
PubMed2005

Identification of genes associated with chemotherapy crossresistance and treatment response in childhood acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) can be cured with combination chemotherapy in over 75% of children, but the cause of treatment failure in the remaining patients is unknown. We determined the sensitivity of ALL cells to individual antileukemic agents in 441 patients and used a genome-wide approach to identify 45 genes differentially expressed in ALL exhibiting crossresistance to prednisolone, vincristine, asparaginase, and daunorubicin. We also identified a distinct phenotype of discordant resistance to asparaginase and vincristine and 139 genes whose expression was associated with this novel phenotype. The expression of these genes discriminated treatment outcome in two independent patient populations, identifying a subset of patients with a markedly inferior outcome (37% +/- 13% 5 year DFS).

Age Factors↗
PubMed2001

In vitro characterization of the hematopoietic system in pediatric patients with acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) has been recognized as a hematologic neoplasia that originates at the level of a primitive lymphoid stem/progenitor cell. To date, however, the biology of the hematopoietic system in this disorder is still not fully understood. In the present study, we have determined the progenitor cell content (including myeloid, erythroid and multipotent progenitors) in 14 children with ALL and followed the proliferation kinetics of these cells in Dexter-type long-term marrow cultures. We have also characterized some aspects related to the composition and function of the hematopoietic microenvironment developed in vitro. All patients included in this study showed extremely reduced levels of progenitor cells (median of 6.2% of the levels found in normal marrow). Proliferation of these cells in long-term cultures was markedly deficient, since they showed very low numbers - compared to normal cultures - and reached undetectable levels after only a few weeks. Regarding the microenvironment developed in vitro, whereas normal marrow samples contained a median of 8 fibroblastic progenitors/10(5) marrow cells and the stromal cell layers developed in culture contained a median of 341000 adherent cells per well, ALL marrow samples showed no fibroblastic progenitors and the numbers of adherent cells were 21% of those in normal cultures. Interestingly, the levels of TNFalpha and IL-6 in ALL culture supernatants were significantly increased, compared to normal cultures. Bone marrow samples from all 14 children were also analyzed once they reached a complete clinical and hematological remission. Myeloid, erythroid and multipotent progenitor cell levels were significantly increased, compared to patients at diagnosis, and proliferation of myeloid progenitors in long-term cultures was also improved. In contrast, proliferation of erythroid progenitors showed no difference to that in cultures from patients at diagnosis. The numbers of fibroblastic progenitors and adherent cells were significantly increased, compared to patients at diagnosis, and TNFalpha and IL-6 levels returned to normal. In summary, in the present study, we have demonstrated significant in vitro alterations of the hematopoietic system, both in terms of its composition and function, in pediatric patients with ALL. Importantly, most of these alterations are corrected, at least partially, after chemotherapy.

Adolescent↗
PubMed1997

Allelic loss in childhood acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most frequent cancer encountered in children. Little is known about the molecular basis of childhood ALL, although the clinical, pathological, and immunophenotypic features have been well documented. To understand the role of tumor suppressor genes (TSGs) in the development of this disease, we performed a detailed allelotype analysis. Twenty-nine patients (24 pre-B and 5 of T-cell lineage) were investigated for loss of heterozygosity (LOH), using 49 highly polymorphic markers distributed over 13 chromosomal arms which are known or postulated to contain TSGs. The highest rates of allelic losses were observed in chromosomes 9p and 12p which were deleted in 29 and 32% of the informative patients, respectively. These are among the most frequent alterations found in childhood ALL. Other losses were found at a lower frequency in chromosomes 6p, 6q, 9q, 17p, and 17q. No LOH was found at chromosomes 3p, 5q, 11p, 11q, 13q and 18q in any patient. These results suggest that many TSGs may be involved in the development of childhood ALL.

Adolescent↗
PubMed2004

Is trisomy 5 a distinct cytogenetic subgroup in acute lymphoblastic leukemia?

Acute lymphoblastic leukemia (ALL) is characterized by recurrent clonal chromosomal abnormalities, with numerical abnormalities being a common feature especially among children. Case reports in the literature suggest that one such recurrent numerical abnormality is the gain of chromosome 5 (trisomy 5) as the sole abnormality; due to the rarity of these cases, however, little is known about their incidence, clinical features, and prognosis. We have identified seven cases with trisomy 5 as the sole or primary chromosomal abnormality from a total of 3,400 karyotypes collected in the Leukaemia Research Fund UK Cancer Cytogenetics Group Karyotype Database. All cases had a precursor B-cell immunophenotype and there was a male predominance. Five patients were children aged between 7 and 14 years old. Four of the six patients with a reasonable follow-up period had relapsed, indicating a poor prognosis. We conclude that trisomy 5 as the sole numerical abnormality occurs predominantly in older children, may be associated with a poor outcome, and may represent a distinct, albeit rare, cytogenetic subgroup in ALL.

Adolescent↗
PubMed2003

[Cytogenetic abnormalities in acute lymphoblastic leukemia].

Acute lymphoblastic leukemias (ALL) represent malignant clonal proliferations of stem cells committed in lymphoid differentiation, B or T-cell ALL. Clonal chromosomal abnormalities are found in 80% children and 70% adult cases. They are associated with an independent prognostic value which modifies the therapeutic approach and therefore karyotyping at diagnosis is mandatory. Molecular techniques such as FISH and RT-PCR are very helpful too as cryptic chromosomal abnormalities have been described. In this review, numerical and structural abnormalities are described: frequency, diagnosis and prognosis value as well as genes involved in structural abnormalities.

B-Lymphocytes↗
PubMedDate not supplied

Soft tissue uptake of Tc99m-MDP in acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is associated rarely with hypercalcemia. This may be due to elevated levels of parathyroid hormone-related peptide (PTHrP). We report a case of an 18-year-old female patient who was presented with a pathological fracture of left intertrochanteric region. Bone scintigraphy was consistent with features of hypercalcemia associated with metastatic calcification. A bone marrow biopsy led to the diagnosis of ALL. The mechanism of hypercalcemia in ALL, metastatic calcification and soft tissue uptake of bone seeking agents in this case are discussed in detail.

Adolescent↗
PubMed1997

Is Mycoplasma Pneumonia associated with childhood acute lymphoblastic leukemia?

Acute lymphoblastic leukemia (ALL) in the childhood peak may be a rare response to delayed first exposure to one or more common infectious agent(s). Mycoplasma Pneumonia has the appropriate socioeconomic correlates and clinical symptoms and the hypothesis that delayed first exposure to it may contribute to ALL is considered. Counts of positive reports of M Pneumonia from disease surveillance data for England and Wales (United Kindom) for 1975-92 have been taken as proxies for community burden of infection. Variation by months of birth (cohort) and diagnosis (period) of incidence of ALL in children born and diagnosed 1975-92 are compared with predictions. When periods were classified by mean M Pneumonia count rate in the nine preceding months, standardized morbidity ratios (SMR) for the highest and lowest 20 percent were 108 and 89 (rate ratio [RR] = 1.2, 95 percent confidence interval [CI] = 1.1-1.4). SMRs for cohorts with highest and lowest predicted risk (i.e., lowest and highest M Pneumonia count rate around birth and during infancy) were 110 and 97 (RR = 1.1, CI = 1.0-1.3). The trend for period was most marked in the cohorts with low opportunity for exposure when young. This ecologic analysis provides preliminary support for the hypothesis.

Analysis of Variance↗
PubMed1997

Microsatellite instability in childhood T cell acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most frequent cancer encountered in children. Little is known about the molecular pathology of childhood T cell ALL. Oncogenesis is a multistep process that involves alterations in proto-oncogenes and tumor suppressor genes. Recently, a mutator phenotype detectable by microsatellite instabilities was shown to be associated with predisposition to cancer. This new mechanism for human carcinogenesis is caused by defects in the DNA replication/repair system. To study the involvement of some of these mutational events in the development of T cell ALL, we have initiated a systematic search for losses of heterozygosity (LOH) and microsatellite instabilities in children affected with this disease. These patients were allelotyped by PCR using 56 microsatellite markers located near known or putative tumor suppressor genes. The microsatellite patterns were altered in more than 80% of the patients. LOH were detected in chromosomes 6p, 12p and 9p. Two third of the patients were deleted for chromosome 9p21, suggesting the involvement of a tumor suppressor gene, probably the p16 gene. The only patient refractory to chemotherapy was shown to be associated with a mutator phenotype. This is the first documented case of a childhood neoplasia associated with genomic instabilities. Our results suggest that defects in DNA replication/repair components are involved in the development of a subset of childhood T cell ALL.

Adolescent↗