Biomedical subjects

S Stass

Publications and source records attributed to S Stass.

At least 19 recordsLinked to original sources

PubMed1998

A geometric study of the amino acid sequence of class I HLA molecules.

HLA class I alleles are studied by representing them in a metric space where each dimension corresponds to each one of the amino acid positions. Their similarity in reference to their ability to present peptides to T cells is then evaluated by calculating the correlation matrix between the amino-acid-composition tables (or binding affinity tables) for the sets of peptides presented by each allele. This correlation matrix is considered an empirical similarity matrix between HLA alleles, and is modeled in terms of possible structures defined in the metric space of HLA class I amino acid sequences. These geometric structures are adequate models of the peptide-binding data currently available. The following clusters of HLA class I molecules are identified in reference to their ability to present peptides: Cluster I) HLA-A3/ HLA-A11/ HLA-A31/ HLA-A33/ HLA-A68; Cluster II) HLA-B35/ HLA-B51/ HLA-B53/ HLA-B54/ HLA-B7; and Cluster III) HLA-A29/ HLA-B61/HLA-B44; the last cluster showing possible similarities between alleles from different loci. In modeling these natural clusters, the geometric structures with more predictive power confirm the importance of those positions in the peptide-binding groove, particularly those in the B pocket. In addition, other positions (46, 79, 113, 131, 144, and 177) appeared to bear some relevance in determining which peptides can be presented by which HLA alleles.

Amino Acid Sequence↗

PubMed1995

Philadelphia chromosome-negative chronic myelogenous leukemia with rearrangement of the breakpoint cluster region. Long-term follow-up results.

BACKGROUND: Five to 10% of patients with chronic myelogenous leukemia (CML) do not have the Philadelphia chromosome (Ph), but one-third of them have rearrangements of the breakpoint cluster region (BCR-positive). METHODS: The authors analyzed the characteristics, treatment response, and prognosis of 23 patients with BCR-positive, Ph-negative CML, and compared them with patients with Ph-positive CML, Ph-negative BCR-negative CML and chronic myelomonocytic leukemia (CMML) treated during the same period. RESULTS: Seventeen patients had early chronic phase CML, 3 had late chronic phase, 2 had accelerated phase, and 1 had blastic phase. The median age was 44 years (range, 14-71 years), median platelet count was 402 x 10(9)/l, and median leukocyte count was 86 x 10(9)/l. Fourteen of the 17 patients with early chronic phase CML received alpha-interferon; 12 (86%) achieved complete hematologic remission. Median survival in chronic phase CML was 60 months (range, 3-90+ months). Patients with Ph-negative BCR-positive CML and those with Ph-positive CML had similar characteristics and outcome. Compared with patients with Ph-negative BCR-negative CML and CMML, patients with Ph-negative BCR-positive CML and Ph-positive CML were significantly younger, had a significantly higher incidence of leukocytosis, thrombocytosis, and peripheral and marrow basophilia, and a significantly lower incidence of anemia, thrombocytopenia, marrow blast percent, and peripheral and marrow monocytosis. The median survival was 60 months for Ph-negative BCR-positive CML, 73 months for Ph-positive CML, 25 months for Ph-negative BCR-negative CML, and 9 months for CMML (P < 0.001). When analyzed adjusting for their stage, patients classified with Ph-negative BCR-positive CML. Stage I disease had a significantly better survival than did patients with Ph-negative BCR-negative CML (P < 0.02). CONCLUSIONS: Patients with Ph-negative BCR-positive CML are similar to those with Ph-positive CML and should be treated with the same approaches.

Adolescent↗

PubMed1995

Change in karyotype between diagnosis and first relapse in acute myelogenous leukemia.

We compared karyotype at first relapse with presenting karyotype in 212 patients with AML seen at MD Anderson Cancer Center (Houston, TX, USA) between 1975 and 1994. In 38% the karyotypes at diagnosis and relapse were identical. A stable karyotype was most frequent (70%) among patients who presented without cytogenetic abnormalities, suggesting that the finding of a normal karyotype is usually not due to sampling error. In contrast, a finding of insufficient metaphases at diagnosis was repeated at relapse in only 6% of cases. A change in karyotype occurred in 67% of 101 patients who presented with an abnormal karyotype and had sufficient metaphases for evaluation at relapse. The great majority of changes involved clonal evolution, clonal devolution (regression), or both; a purely normal karyotype and unrelated clones were seen in 11 and three of the 101, respectively. Change in karyotype between diagnosis and relapse and type of change were unrelated to remission duration. The only group in which karyotype at relapse vs that at diagnosis had a possible bearing on achievement of second CR were patients who presented with abnormalities other than inv(16), t(8;21) or t(15;17) and who at relapse had only normal metaphases; such patients had higher CR rates than comparable patients who retained their presenting abnormalities.

Chromosome Aberrations↗

PubMed1994

2-Chlorodeoxyadenosine therapy in patients with T-cell lymphoproliferative disorders.

Mature T-cell lymphoproliferative disorders comprise a heterogenous group of diseases for which there is no standard therapy. These disorders are uncommon, and are usually treated similarly to their B-cell counterparts, but with less success. Nucleoside analogues have proven effective in indolent B-cell disorders but have been less well explored in T-cell malignancies. We treated 22 patients with mature T-cell lymphoproliferative diseases with 2-chlorodeoxyadenosine (2-CDA) administered as a continuous infusion at a daily dose of 4 mg/m2 over 7 days. Nineteen of the patients had received prior therapy with a median number of prior regimens of three. Eleven patients had leukemia or large granular lymphocytosis, eight patients had mycosis fungoides, and three had T-cell lymphoma. Nine patients (41%) responded to 2-CDA. Four of the patients had responses that were complete remissions, and three of these four patients remain in remission at 23, 24, and 23 months. The only important toxic effects were fever or infection, seen during 38% of courses. In conclusion, 2-CDA appears to be an effective therapy in T-cell lymphoproliferative disorders and deserves wider evaluation in this subset of patients.

Adult↗

PubMed1994

All-trans retinoic acid followed by chemotherapy for salvage of refractory or relapsed acute promyelocytic leukemia.

BACKGROUND: All-trans retinoic acid (ATRA) is effective in the treatment of relapsed or refractory acute promyelocytic leukemia (APL), but relapse is the rule if response is unmaintained. METHODS: Seventeen patients with APL were salvaged with ATRA at a dosage of 50 mg/m2/day for 3 months or until complete remission (CR) was achieved; idarubicin (12 mg/m2/day for 4 days) was added if blast plus promyelocyte count either was or reached > or = 10 x 10(3)/microliters. After CR was achieved, patients received three courses of idarubicin (12 mg/m2 daily for 3 days) followed by three courses of mitoxantrone (5 mg/m2 daily for 3 days) and etoposide (250 mg/m2 daily for 3 days). Maintenance was with 6-mercaptopurine and methotrexate. RESULTS: A CR was achieved in 14 patients (82%), the disease was refractory in 2 patients, and one patient died during induction. Three patients underwent allogeneic bone marrow transplant during CR. After a median follow-up of 26 weeks, six patients remain in CR. Median CR duration is 40 weeks (range 8-56+). Patients treated with ATRA plus chemotherapy in first salvage, when compared to a historic control group treated with chemotherapy alone, had a significantly better CR rate (87% vs. 57%; P = 0.04) and a lower induction death rate (7% vs. 29%; P = 0.08), resulting in longer median survival (26 vs. 17 weeks; P = 0.13). Four patients developed the "retinoic acid syndrome", which was fatal in one case. Three patients developed thrombotic events. CONCLUSIONS: ATRA followed by chemotherapy is effective treatment for patients with APL who relapse after conventional therapy, and it may be superior to chemotherapy alone.

Adolescent↗

PubMed1994

Abnormalities in the long arm of chromosome 11 (11q) in patients with de novo and secondary acute myelogenous leukemias and myelodysplastic syndromes.

Leukemias with abnormalities in chromosome 11q23 occur frequently after exposure to topoisomerase II-reactive drugs. We investigated the characteristics and outcome of patients with de novo or secondary acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) with abnormalities in chromosome 11q. Sixty-one patients had 11q abnormalities. Alterations involved 11q23 in 38 patients and other 11q abnormalities in 23. Sixteen patients had secondary disease, 12 involving 11q23, and four with other 11q abnormalities; 26 patients with de novo disease had 11q23 abnormalities and 19 other 11q abnormalities. The most common 11q23 abnormality was t(9;11), significantly more common in secondary (9/12) than in de novo (6/26) leukemias (p = 0.003). There were no significant differences in clinical characteristics between de novo and secondary groups involving 11q23. Five of 12 patients (42%) with secondary and 20/26 (77%) with de novo disease achieved complete remission (p = 0.05). Median survival was 6 weeks in the secondary group and 71 weeks in the de novo group (p = 0.001). There were no long-term survivors in either group. Results are similar when other 11q abnormalities are included. Adults with AML or MDS with 11q abnormalities secondary to prior chemotherapy have a worse prognosis than patients presenting de novo. However, 11q abnormalities define a population with a poor prognosis even when presenting de novo.

Adolescent↗

PubMed1992

Response assessment in chronic lymphocytic leukemia after fludarabine plus prednisone: clinical, pathologic, immunophenotypic, and molecular analysis.

The goals of this study were to evaluate the response to treatment in chronic lymphocytic leukemia (CLL) according to clinical, pathologic, immunophenotypic, and molecular features, as well as to address the clinical significance of each finding. One hundred fifty-nine CLL patients with either advanced Rai stage III or IV (81 patients) or progressive Rai stage 0 to II (78 patients) were treated with fludarabine (30 mg/m2/d intravenously every day for 5 days) plus prednisone (30 mg/m2/d orally daily for 5 days). Thirty-six patients were previously untreated. The response rates were 12% complete response (CR), 30% nodular complete response (nCR), and 18% partial response (PR). In all patients who achieved a complete response (both CR and nCR) less than 30% of nucleated cells were lymphocytes on marrow aspirate differential analysis; however, nCR patients had residual nodular and/or interstitial lymphocyte involvement on marrow biopsy examination. There was no evidence of leukemic infiltration on marrow biopsy examination in CR patients. With a median follow-up of 35 months, comparison of time to progression in the CR and nCR groups at 2 years showed a projected 87% versus 55% progression-free survival (P less than .03). Residual disease assessment by flow cytometry using simultaneous dual-color staining on blood and marrow lymphocytes was also performed on each patient. Residual disease was determined by the expression of CD5 on B lymphocytes and the monoclonality of surface light-chain expression. After six courses of fludarabine plus prednisone, no residual disease was detected by flow cytometry in 89% of the CRs, 51% of the nCRs, and 19% of the PRs. Clinical residual disease in PR patients with no residual disease detectable by flow cytometry was limited to lymph-adenopathy. Time to progression at 2 years was longer in CR and nCR patients having no residual disease detected by flow cytometry (84% v 39% 2-year progression-free survival, P less than .001). Posttreatment lg gene rearrangement analysis using JH, J kappa, and C lambda probes demonstrated no rearranged bands and a return to the germline configuration in five of seven CRs and two of eight nCRs studied. The molecular studies were concordant with the dual-parameter immunophenotype results and none of the patients who reverted to a germline DNA pattern after treatment have experienced relapse. The absence of detectable minimal residual disease by bone marrow biopsy, dual-color flow cytometry, and lg gene rearrangement analysis is achieveable in CLL with fludarabine and is predictive of the response duration.

Adult↗

PubMed1992

Polyclonal hematopoiesis in interferon-induced cytogenetic remissions of chronic myelogenous leukemia.

Interferon (IFN) therapy of early chronic myelogenous leukemia (CML) frequently produces partial or complete cytogenetic remission of the disease. Patients with complete cytogenetic remission often continue on therapy for several years with bone marrow showing only diploid (normal) metaphases. We studied hematopoiesis in five female patients with major cytogenetic remissions from CML during IFN therapy. Clonality analysis using the BstXI PGK gene polymorphism showed that granulocytes were nonclonal in all patients during cytogenetic remission. BCR region studies showed rearrangement only in the one patient whose remission was incomplete at the time of sampling. Granulopoiesis is nonclonal in IFN-induced remissions of CML and may be derived from normal hematopoietic stem cells.

Clone Cells↗

PubMed1992

Detection of minimal residual disease by polymerase chain reaction of bcr/abl transcripts in chronic myelogenous leukaemia following allogeneic bone marrow transplantation.

The prognostic significance of detecting minimal residual disease by polymerase chain reaction (PCR) amplification of bcr/abl mRNA transcripts was investigated in 27 bone marrow samples from 20 patients with Philadelphia chromosome (Ph1) positive chronic myelogenous leukaemia (CML) in complete cytogenetic remission following allogeneic bone marrow transplantation. Sixteen were transplanted in first chronic phase, two were in second chronic phase, one was in accelerated phase and one was in blast crisis. All 20 achieved complete cytogenetic remission post transplant and 15 patients had detectable bcr/abl mRNA by PCR from 2 to 22 months following the procedure. One of these patients had graft failure and one died from graft-versus-host-disease at 7 months. Of the remaining 13 PCR-positive patients, only one (8%) relapsed after 23 months; the other 12 were alive and still in remission after a median follow-up of 16+ months (ranging 5+ to 29+ months). Five patients were PCR negative; all are alive in complete clinical and cytogenetic remission at 10+, 11+, 19+, 25+ and 25+ months post transplant. In this study, detection of subclinical Ph1-positive cells by PCR was not associated with imminent clinical or cytogenetic relapse. Since late recurrence may potentially occur, long-term follow-up is required to definitely determine the prognostic value of the PCR assay.

Adult↗

PubMed1992

AML-associated cytogenetic abnormalities (inv (16), del (16), t(8;21)) in patients with myelodysplastic syndromes.

Evidence suggests that prognosis in patients with myelodysplastic syndromes (MDS) or acute myelogenous leukemia (AML) depends more on karyotype than on formal classification as either MDS or AML according to the French-American-British (FAB) system. We provide further evidence of overlap between these two entities, reporting 4 patients who presented with either inv(16) (p13q22), del(16) (q22), or t(8;21) despite an FAB diagnosis of MDS rather than the diagnosis of AML with which these abnormalities are generally associated. In 3 patients, disease was relatively long-standing (3-10 months) prior to diagnosis, suggesting that the association between MDS and these cytogenetic abnormalities may not merely reflect a transient phenomenon. Two patients with inv(16) and the MDS subtype refractory anemia with excess blasts in transformation (RAEB-t) received AML-type chemotherapy as did a patient with t(8;21) and RAEB-t. All entered CR paralleling the high CR rate seen in patients with AML and these abnormalities. Our data support the concept that MDS and AML may be different manifestations of the same disease.

Adolescent↗

PubMed1991

Significance of the P210 versus P190 molecular abnormalities in adults with Philadelphia chromosome-positive acute leukemia.

We investigated the significance of p210 and p190 molecular abnormalities in 32 adults with Philadelphia chromosome (Ph)-positive acute leukemia. p210 was detected in 15 patients (47%), p190 in 16 (50%), and both in one (3%). p210 was noted in 11 of 24 patients (46%) with acute lymphocytic leukemia, and in four of eight patients (50%) with acute myelogenous or undifferentiated leukemia. Among 29 patients with untreated disease (p210, 14 patients; p190, 15 patients), no significant differences in the two molecularly distinct groups were observed by pretreatment characteristics including age, degree of organomegaly, anemia, leukocytosis, thrombocytopenia, occurrence of karyotypic abnormalities in addition to Ph, or residual diploid metaphases. Complete response (CR) rates were also similar. Although the remission duration tended to be longer with p190 (P = .08), the differences were minor (median duration 29 v 20 weeks) and not paralleled by differences in survival rate. In 10 patients studied by karyotypic analysis in remission, two of four patients with p190 and two of six patients with p210 showed 100% normal metaphases. One of the seven patients (14%) with p210 who achieved CR manifested a morphologic picture of second chronic-phase chronic myelogenous leukemia lasting for 1 month. We conclude that the molecular studies in Ph-positive acute leukemia are not associated with significantly different clinico-laboratory, karyotypic, or prognostic implications.

Adult↗

PubMed1990

Mixed-lineage leukemia revisited: acute lymphocytic leukemia with myeloperoxidase-positive blasts by electron microscopy.

Seven adult patients with untreated acute lymphocytic leukemia (ALL) who manifested 5% to 40% myeloperoxidase (MPO)-positive blasts by electron microscopy (EM) are reported. Six patients had an L2 morphology, and one had an L1 morphology by the French-American-British (FAB) classification. The immunophenotype was T cell in four patients. Molecular analysis showed rearrangement of the immunoglobulin JH in four patients, three of them also having rearrangement of the T-cell receptor beta or gamma. Induction chemotherapy with vincristine-doxorubicin-dexamethasone (VAD) produced a complete remission in five of six patients (83%). Our findings suggest the existence of a previously undescribed subtype of mixed-lineage leukemia, which by morphology and immunophenotype often appears as T-cell ALL but exhibits MPO-positive blasts by EM.

Adolescent↗

PubMed1989

Rhabdomyosarcoma, presenting as disseminated malignancy from an unknown primary site: a retrospective study of ten pediatric cases.

From 1962-1984, ten children were referred to St. Jude Children's Hospital with a metastatic poorly differentiated malignancy; extensive diagnostic workup had failed to disclose the site of the primary tumor. Multiple skeletal metastases as well as bone marrow involvement were common findings. Erythrocytes were detected in the cytoplasm of tumor cells in several cases, and cytochemical stains confirmed that these phagocytic cells did not have features of mononuclear phagocytes. Establishing a pathologic diagnosis in these cases was difficult, and most special studies including cytochemistry and electron microscopy were not helpful in elucidating the diagnosis. A diagnosis of rhabdomyosarcoma was made at presentation in six cases. In the remaining cases, the diagnosis of rhabdomyosarcoma was subsequently made after rebiopsy of new tumor masses during the course of the illness, by ultrastructural examination of a cell line derived from the tumor or at postmortem examination. Based on initial symptoms, clinical features, and postmortem findings, the primary tumor sites were assumed to be in the middle ear, paravertebral area, base of skull, retrobulbar space, chest wall, and retropancreatic area. In four patients the disease was confined to bone marrow, lymph nodes, and meninges so that a primary site could not be assigned. The approach to pediatric patients presenting with disseminated malignancy from an occult primary site should consist of an aggressive pursuit of a specific diagnosis and establishment of a primary site to better direct therapy, particularly for those children whose tumors may be responsive to specific therapy.

Adolescent↗

PubMed1987

DNA aneuploidy in adult acute leukemia.

Using flow cytometric techniques, we determined DNA ploidy levels in the bone marrow of 318 successive adult patients with newly diagnosed acute leukemia. Overall, 26% exhibited DNA stem line abnormalities, usually with a 10%-15% DNA excess, regardless of morphologic diagnosis. DNA aneuploidy was seen most frequently in patients with a hyperdiploid chromosome number and karyotype instability (50%), but was also present in a third of patients with chromosomal translocations and in 20% of patients with a normal diploid karyotype. Thus, among 73 patients with DNA aneuploidy, quantitatively concordant karyotype abnormalities were observed in almost 40% of patients; the discrepancy between DNA content and chromosome number in the remaining patients may reflect differences in the cell cycle position of target cells in G1/0 phase or mitosis, respectively. Cytogenetics affected treatment outcome in acute myelogenous leukemia (AML) with more favorable short- and long-term prognosis among patients with translocations compared with those with numeric abnormalities. The presence of an abnormal DNA stem line, among AML patients with translocations, identified a favorable subgroup with significantly longer remission duration and survival (25 and 26 months versus 18 and 13 months, respectively). In addition, the prognostic implications of DNA aneuploidy in AML were age-dependent, in that favorable effects among patients with translocations and unfavorable effects among those with numeric abnormalities or diploid karyotypes were most obvious in young and not in older patients (greater than or equal to 40 years). In adults with ALL, DNA aneuploidy was associated with shorter survival (15 versus 39 months in the diploid group), an observation that is distinctly at variance with recent findings in childhood ALL. Our results indicated that DNA flow cytometry was complementary to standard cytogenetics for the detection of genomic abnormalities; and DNA aneuploidy emerged, like in children but not in adults with ALL, as a new favorable prognostic feature in a subgroup of adults with AML, the biologic basis of which remains to be determined.

Adult↗

PubMed1987

Localization of an abundant myeloid mRNA to individual leukocytes in mixed cell populations.

Differential screening of cDNA libraries with radiolabeled RNAs isolated from various sources provides a convenient way to identify cDNA clones representing RNAs that are more (or less) abundant in selected tissues. This strategy was previously used to isolate cDNA clones representing poly(A+)RNAs (mRNA) that are abundant in leukocytes from chronic myelogenous leukemia (CML) patients. One limitation with the initial experiments was that the RNAs were isolated from heterogenous cell populations and it was impossible to distinguish whether all of the cells were producing the abundant mRNAs or if a subset of the cell population was responsible for the majority of the RNA species. To resolve this important issue, we have directly hybridized radiolabeled cDNAs to the cellular RNAs of intact, morphologically distinguishable, primary hematopoietic cells. In the present study clone pC-A3, which represents an mRNA species that is abundant in the chronic phase of CML, was used to examine three samples from normal bone marrow, one sample from normal peripheral blood, and four samples from peripheral blood of leukemic patients (one Ph1 + AL, two CML in compensated phase, and one CML in accelerated phase). The results show that while C-A3 gene expression is detectable in cells from the granulocytic, monocytic, and lymphoid lineage, its relative abundance peaks at the level of the neutrophilic myelocytes and promyelocytes. Earlier myeloid precursors like myeloblasts or mature neutrophilic granulocytes show less labeling. Further, all maturation stages of eosinophils (Eos) and basophil (Baso) are highly labeled. This finding reinforces recent evidence that Eos and Baso share a common progenitor and suggests that these two cell types may have a stronger role than previously noted in the prominent myeloproliferative response that is characteristic of CML.

Basophils↗

PubMed1987

Childhood monosomy 7 syndrome: clinical and in vitro studies.

The clinical and cell growth characteristics of 11 children with monosomy 7 presenting as preleukemia (eight cases) or acute nonlymphoblastic leukemia (three cases) were studied. Anemia was common to all patients, with nine showing leukocytosis, seven thrombocytopenia, and one thrombocytosis. There was a striking predominance of males (M/F ratio, 10:1) and a young median age (3 years). Preleukemia evolved to acute nonlymphoblastic leukemia in five patients and to myelofibrosis in one. In vitro studies of bone marrow progenitor cells cultured in leukocyte feeder-stimulated agar revealed abnormal cell proliferative patterns, most often an increased number of small clusters, for all 11 subjects. The cells of some preleukemic patients showed increased growth even in the absence of an exogenous source of colony-stimulating factor, suggesting autonomous growth or possibly autocrine stimulation. Combination chemotherapy or bone marrow transplantation failed to induce complete remission in the seven patients who were treated. Our findings in these 11 cases confirm the poor prognosis of monosomy 7 presenting as preleukemia in children. The in vitro studies suggest an association between altered cell growth in vitro and clinical evolution to frank leukemia.

Acute Disease↗

PubMed1986

Phagocytic activity and expression of myeloid-associated cell surface antigens by blast cells in acute lymphoblastic leukemia.

The malignant cells of patients with acute lymphoblastic leukemia (ALL) rarely show phagocytic activity. In this retrospective survey, blasts from 7 of 196 patients with newly diagnosed ALL demonstrated phagocytic activity toward platelets and erythrocytes. The morphology and cytochemical staining properties of the cells were typical of ALL. Immunophenotyes were those of common ALL (CALLA+, HLA-DR+) for six patients and of pre-B-cell ALL (positive cytoplasmic immunoglobulin) for one. However, blast cells from six of the seven patients also reacted with myeloid-associated monoclonal antibodies (MCS.2 and/or SJ-D1). The wide overlap in the percentages of blasts expressing CALLA and those expressing myeloid-associated antigens suggests that some cells possessed both lymphoid- and myeloid-associated surface antigens. By a dual staining technique, two patients tested had blasts expressing antigens of both lineages. Each child achieved a complete remission after treatment with agents effective for ALL and remains in remission for 13+ to 20+ months. These morphologic and immunologic findings may define a distinct subtype of acute leukemia.

Acute Disease↗

PubMed1986

Biologic and prognostic significance of the presence of more than two mu heavy-chain genes in childhood acute lymphoblastic leukemia of B precursor cell origin.

We examined the arrangement of the mu heavy-chain immunoglobulin (Ig) genes in the leukemic blast cell DNA of 93 children with acute lymphoblastic leukemia (ALL). All cases met morphologic and cytochemical criteria for ALL, lacked detectable T cell surface antigens, and expressed HLA-DR (Ia) antigens. Eighty-three of the 93 patients (89%) were positive for the common acute lymphoblastic leukemia antigen (CALLA), and 20 of 91 (22%) tested had detectable cytoplasmic immunoglobulin. As expected, the heavy-chain lg gene was rearranged in all cases, and the pattern of rearrangements was variable; 23 had one allele rearranged and one in the germ line configuration; 15 had one rearranged and one deleted; and 37 had two rearranged. Unexpectedly, in 18 patients the presence of more than two mu gene-hybridizing bands was detected. Combinations of enzymes and heavy-chain gene probes were used to confirm that the extra bands were not the result of underdigestion of the DNA or DNA restriction site polymorphism. In eight of the 18 patients, we identified an extra chromosome 14 as a possible cause of the extra bands' hybridizing to the mu heavy-chain constant-region probe. In the remaining ten patients, the presence of three or four bands hybridizing with the mu probe suggests the presence of two populations of leukemic cells that may have arisen either by separate leukemic transformation events or by clonal evolution of one clone into two related lines. Although preliminary (2-year follow-up), our data suggest that childhood ALL of B lineage with more than two mu heavy-chain genes, but without extra copies of chromosome 14, may be more resistant to therapy.

Adolescent↗