Biomedical subjects

F G Behm

Publications and source records attributed to F G Behm.

At least 145 records · Page 8Linked to original sources

PubMed1990

Morphologic and cytochemical characteristics of childhood lymphoblastic leukemia.

The majority of childhood acute leukemias can be classified as acute lymphoblastic leukemia and acute nonlymphocytic leukemia with light microscopy and cytochemical stains alone. However, myeloperoxidase-negative myeloblastic leukemias and megakaryoblastic leukemias, as well as some metastatic tumors, can mimic lymphoblastic leukemia when these cytologic examinations are used. Conversely, occasional cases of Sudan black B-positive ALL can be confused with myeloblastic leukemia. Thus, additional immunologic and sometimes further ultrastructural studies should complement the morphologic diagnosis of ALL. The significance of L1 and L2 subtypes of ALL is still controversial. Modern chemotherapy may have obscured any significance of this division. Future studies of lymphoblast morphology should center on biologic correlates of the L2 cytology. Little prognostic significance has been found for the morphologic variants of ALL, such as the granular and hand-mirror cell types. It is important not to confuse granular ALL with acute myeloblastic leukemia. Functional immunologic studies may help in delineating the cause of uropod formation in hand-mirror variant ALL.

Blood Cells↗

PubMed1990

Presenting features and treatment outcome of adolescents with acute lymphoblastic leukemia.

Adolescents had lower rates of remission induction and shorter event-free survival than younger children in this study of consecutively treated patients with acute lymphoblastic leukemia (ALL). When compared to the younger patients (ages 1-9 years; n = 995), adolescents (ages 10-21 years; n = 338) were significantly more likely to have adverse prognostic features, including T cell phenotype, L2 blast cell morphology, higher serum lactate dehydrogenase level, higher leukocyte count, leukemic cell DNA index less than 1.16, and ploidy other than hyperdiploidy greater than 50. Within the adolescent group, outcome was worse for those older than 15 years. The increased frequency of unfavorable clinical and biologic features undoubtedly accounts in part for the poorer prognosis of adolescents with ALL. However, the independent prognostic significance of age greater than or equal to 10 years suggests that as yet unknown factors contribute to treatment failure in adolescent patients.

Adolescent↗

PubMed1989

Secondary acute myeloid leukemia in children treated for acute lymphoid leukemia.

We studied the risk of the development of acute myeloid leukemia (AML) during initial remission in 733 consecutive children with acute lymphoid leukemia (ALL) who were treated with intensive chemotherapy. This complication was identified according to standard morphologic and cytochemical criteria in 13 patients 1.2 to 6 years (median, 3.0) after the diagnosis of ALL. At three years of follow-up, the cumulative risk of secondary AML during the first bone marrow remission was 1.6 percent (95 percent confidence limits, 0.7 and 3.5 percent); at six years, it was 4.7 percent (2 and 10 percent). The development of secondary AML was much more likely among patients with a T-cell than a non-T-cell immunophenotype (cumulative risk, 19.1 percent [6 and 47 percent] at six years). Sequential cytogenetic studies in 10 patients revealed entirely different karyotypes in 9, suggesting the induction of a second neoplasm. In eight of these patients, the blast cells had abnormalities of the 11q23 chromosomal region, which has been associated with malignant transformation of a pluripotential stem cell. There was no evidence of loss of DNA from chromosome 5 or 7, a karyotypic change commonly observed in cases of AML secondary to treatment with alkylating agents, irradiation, or both. We conclude that there is a substantial risk of AML in patients who receive intensive treatment for ALL, especially in those with a T-cell immunophenotype, and that 11q23 chromosomal abnormalities may be important in the pathogenesis of this complication.

Adolescent↗

PubMed1989

Cytogenetics of childhood acute nonlymphocytic leukemia.

Interest in more precise subclassification of the acute leukemias by cytogenetic criteria led us to identify and characterize the full range of chromosomal abnormalities in 121 children with de novo acute nonlymphocytic leukemia (ANLL). Only 21% of the cases had normal karyotypes; 62% had consistent or recurrent alterations, most commonly inv(16) or del(16), t(8;21), t(15;17), t(9;11), t(11;V) or del(11), and -7 or 7q-; and 17% had miscellaneous, apparently random, clonal abnormalities. Statistically significant associations between chromosomal abnormalities and the morphologic/cytochemical subtypes of ANLL, defined by criteria of the French-American-British (FAB) cooperative group were demonstrated for the t(8;21) in M1 and M2 leukemia, t(15;17) in M3, t(9;11) in M5, and translocations involving 11q23 other than t(9;11) [t(11;V)] or del(11q) in M4 and M5. The chromosome 16 inversion was not restricted to the M4 subtype, as is generally reported, and was not uniformly associated with increased and/or abnormal marrow eosinophils. None of these 121 cases were characterized by the Philadelphia chromosome, nor did any have the t(6;9), t(16;16), or inv(3), which have been noted previously in this disease. In addition to confirming several recognized correlations between recurrent structural chromosome abnormalities and FAB subtypes, this study identified novel abnormalities that have not been reported by others. It also disclosed an unusual heterogeneity of chromosome 16 abnormalities with respect to their distribution among FAB subtypes, their association with marrow eosinophilia, and their participation with other chromosomes in translocations.

Child↗

PubMed1989

Childhood acute lymphoblastic leukemia with chromosomal breakpoints at 11q23.

Twenty-one (5.7%) of 368 cases of acute lymphoblastic leukemia (ALL), studied fully for karyotype and immunophenotype, had breakpoints in the q23 region of chromosome 11. This abnormality resulted from reciprocal translocation in 17 cases [with chromosomes 4 (n = 5), 10 (n = 2), and variable chromosomes (n = 10)], from deletions in three cases, and from a duplication in one case. The 17 children with 11q23 translocations had higher leukocyte counts (P less than .01) and were more likely to be black (P less than .01) and younger (P = .08) as compared with each of the following non-11q23 translocation groups: t(1;19), t(9;22), random translocations, and cases without translocations. Event-free survival at 3 years for the 11q23 translocation group did not differ significantly from that of the t(1;19), t(9;22), or random translocation groups. Leukemic cells from ten of the 21 patients with an 11q23 structural chromosomal abnormality had an immunophenotype indicative of B-lineage ALL (HLA-DR+, CD19+, CD2-, CD3-); this was confirmed by the presence of rearranged immunoglobulin heavy-chain genes in seven cases. In eight of these ten B-lineage cases, the blasts were negative for expression of the CD10 antigen, indicating a primitive stage of B-cell development. Four cases were classified as T-cell ALL, and seven others were characterized by blasts that failed to react with our panel of lineage-associated monoclonal antibodies (MoAbs). Myeloid antigens were expressed by leukemic cells in three of the cases that were tested. The initial clinical features associated with translocations involving the 11q23 chromosomal region may define a distinct subtype of ALL. Whether the constellation of findings relates to a breakpoint at 11q23 per se or to the specific translocation will require further study.

Chromosome Aberrations↗

PubMed1989

Two karyotypically independent leukemic clones with the t(8;21) and 11q23 translocation in acute myeloblastic leukemia at relapse.

Leukemic blast cells are thought to arise from clonal expansion of a single transformed hematopoietic cell. This generality is supported by the rarity of convincing reports on acute myeloblastic leukemia (AML) with two karyotypically independent clones. Relying on sequential cytogenetic analyses, we identified such clones in two children with relapsed AML. The first case, classified as M2 leukemia in the French-American-British (FAB) classification system, had a t(8;21) (q22;q22) at diagnosis; 16 months later, at relapse, the leukemic cells had uniform morphologic features similar to those observed at diagnosis, except that two independent clones were present: one with the original t(8;21) and the other with t(11;22)(q23;q13) [corrected]). The second case was initially classified as FAB M1 leukemia with a t(8;21) (q22;q22). At relapse, 16 months later, the blast cells appeared morphologically uniform and similar to the diagnostic specimen; however, in addition to the original t(8;21) clone, there was a t(1;11) (p32;q23) [corrected]. These findings suggest that separate leukemogenic events affecting different progenitor cells can occur in rare cases of AML. The presence of two karyotypically independent clones could also be explained by multistep leukemogenesis; that is, more than one cell from a common pool of preleukemic cells could be affected by the transforming event, resulting in two independent clones. Alternatively, in light of recent reports of therapy-related leukemias with an 11q23 translocation, the new independent clone in these two patients could represent a therapy-related secondary malignancy. Thus, 11q23 translocations may occur preferentially in stem cells that are more susceptible to treatment-induced malignant transformation.

Adolescent↗

PubMed1989

Malignancy in the neonate.

From January 1962 to July 1988, 34 infants less than 29 days of age who had cancer were seen at St. Jude Children's Research Hospital (SJCRH). The malignancies in this group consisted of 19 neuroblastomas, 6 leukemias, 3 retinoblastomas, 2 Wilms' tumors, 2 melanomas, and 2 teratomas. Twenty-three patients (68%) are alive and free of disease 2 months to 24 years after diagnosis. We reviewed the presentation and initial symptoms, pathology reports, patient population, associated anomalies, potential genetic influences, and possible perinatal factors. The most common initial symptom was an enlarging abdomen or abdominal mass. Pathological findings were occasionally difficult to interpret; five additional infants who were referred to us did not have malignancies. There was no increased incidence of associated anomalies or perinatal insults. The only genetic factor was retinoblastoma in one parent of each infant diagnosed as having retinoblastoma. The possible etiology of neonatal tumors is discussed.

Humans↗

PubMed1989

Clonal analysis of childhood acute lymphoblastic leukemia with "cytogenetically independent" cell populations.

Acute lymphoblastic leukemia (ALL) is generally regarded as a clonal disease in which a single abnormal progenitor cell gives rise to neoplastic progeny. Five of 463 cases of childhood ALL with adequately banded leukemic cells were found to have two cytogenetically independent cell populations. In addition, two of the four cases tested had more than two rearranged immunoglobulin genes and (or) T cell receptor genes. To investigate the clonality of these unusual leukemias, we examined the neoplastic cells for X-linked markers extrinsic to the disease. Leukemic cells from each of the three patients heterozygous for an X-linked, restriction fragment length polymorphism showed a single active parental allele, suggesting that both apparently independent cell populations developed from a common progenitor. These cases provide evidence that leukemogenesis involves a multistep process of mutation and suggest that karyotypic abnormalities may be a late event of malignant transformation.

Alleles↗

PubMed1989

Nonrandom abnormalities of chromosome 9p in childhood acute lymphoblastic leukemia: association with high-risk clinical features.

To assess the frequency and significance of nonrandom abnormalities of chromosome 9p in childhood acute lymphoblastic leukemia (ALL), we analyzed our experience with 398 consecutive cases with completely banded karyotypes. Forty cases (10%) with abnormalities of 9p were identified: 26 with deletions, nine with unbalanced translocations resulting in the loss of 9p material, and five with apparently balanced reciprocal translocations. As compared with children with ALL lacking 9p abnormalities, these 40 cases were significantly older, had higher initial circulating WBC counts, more "lymphomatous" disease characteristics (including presence of a mediastinal mass in 15%. T-cell phenotype in 26%, splenomegaly greater than 8 cm in 25%), an increased failure rate in the first 2 to 3 years after diagnosis, and a higher incidence of extramedullary relapse. Conversely, lymphomatous ALL cases were twice as likely (19% v 8%) to have an abnormality of chromosome 9p than ALL cases lacking lymphomatous features (P = .01). The finding of an abnormal chromosome 9p, however, was not specific for lymphomatous ALL or T-cell lineage, because most cases were neither lymphomatous nor T-cell, and the overall Kaplan-Meier distribution of treatment failures for abnormal 9p cases was not statistically significantly different from control ALL cases receiving the same treatment who lacked abnormalities of 9p (P = .06, by log-rank test). We conclude that nonrandom abnormalities of chromosome 9p, especially a breakpoint in 9p21-22, occur with increased frequency in childhood ALL in association with some high-risk clinical features. Despite this association, the chromosome anomaly is nonspecific in its syndrome delineation and confers no major adverse consequence on long-term survival of childhood ALL treated with modern therapy. However, due to an apparently increased hazard of involvement of the CNS (eight of 17 failures), it may be inadvisable to lessen the intensity of CNS preventive therapy for this group of patients.

Child↗

PubMed1988

Chromosome analysis of 30 cases of non-Hodgkin's lymphoma.

Karyotype analysis is now a routine procedure in the clinical evaluation of leukaemia because of its value in diagnosis and prognosis. This is not yet so for lymphoma because the relative paucity of data available has prevented an evaluation of its usefulness. We therefore karyotyped 30 unselected cases of non-Hodgkin's lymphoma and six controls with reactive hyperplasia. All cases were karyotyped 'blind' to diagnosis; all were classified by immunohistopathology and 29 were analysed before treatment. This is one of the four largest cytogenetic studies to be reported of untreated, immunotyped patients with non-Hodgkin's lymphoma. Chromosome abnormalities were observed in 29/30 tumour samples. The only rearrangement observed more than once was the 14;18 translocation. The combined results of this study and others indicate that while there are no unique associations between histological sub-types and chromosome rearrangements in untreated non-Hodgkin's lymphoma patients, some partial specificity does exist.

Adolescent↗

PubMed1988

Correlation of karyotype and immunophenotype in childhood acute lymphoblastic leukemia.

To correlate leukemic cell karyotype with immunophenotype, we studied 364 children with acute lymphoblastic leukemia (ALL). A prognostically favorable cytogenetic feature, hyperdiploidy greater than 50 chromosomes, was found in 33% of cases classified as common ALL antigen positive (CALLA+) early pre-B (common) ALL, in contrast to 18% of pre-B cases (P = .012), 5% of T cell cases (P less than .001), and none of the B cell cases (P less than .001) or cases of CALLA negative (CALLA-) early pre-B ALL (P = .002). The frequency of translocations, an adverse cytogenetic feature, was significantly lower in CALLA+ early pre-B ALL cases (35%) than in B cell (100%; P less than .0001), pre-B (59%; P less than .001), or CALLA- early pre-B (62%; P = .016) cases. Thus, patterns of chromosomal change differ widely among the major immunophenotypic groups of ALL and may account for reported differences in responsiveness to treatment.

Antigens, Neoplasm↗

PubMed1988

Serum interleukin 2 receptor levels in childhood acute lymphoblastic leukemia.

The clinical significance of interleukin 2 receptor (IL2R) concentrations in serum was determined for 344 children with newly diagnosed acute lymphoblastic leukemia (ALL). Serum levels of IL2R in patients (267 to 80,000 U/mL, median 2,007 U/mL) were significantly higher than normal control values (170 to 738 U/mL, median 347 U/mL) (P less than .0001). Measurements in cases of T cell ALL were lower than in the non-T, non-B cases (P = .02). Among the 264 patients with non-T, non-B ALL, but not in those with T cell disease, higher serum IL2R levels (greater than 2,000 U/mL) were associated with a poorer treatment outcome (P = .04). In a multivariate analysis, serum IL2R level contributed independent prognostic information beyond that conveyed by leukocyte count, race, and age (P = .04). One explanation for these results is that soluble IL2R competes with normal lymphocyte-integrated IL2R for the ligand and thus could suppress host antitumor immunity.

Adolescent↗

PubMed1988

Acute myeloid leukemia with T-lymphoid features: a distinct biologic and clinical entity.

We studied the clinical and biologic features of 10 cases of acute leukemia that met standard French-American-British (FAB) criteria for acute myeloid leukemia (AML) but in which the blast cells also expressed the T-cell-associated CD2 surface antigen. All cases had greater than 3% myeloperoxidase and Sudan black B-positive leukemic blasts, and blasts from seven cases contained Auer rods. Reactivity of the cells with a panel of monoclonal antibodies (MAbs) indicated that leukemic cells in all cases expressed myeloid-associated (CD11b, CD13) surface antigens, further supporting the diagnosis of AML. However, blasts from every patient coexpressed the T-cell-associated surface CD2 and CD7 as well as cytoplasmic CD3 antigens. Blasts from five patients expressed surface CD25, whereas blasts from only one expressed surface CD3. Five patients had rearranged T-cell receptor beta-chain genes, whereas only three had rearranged T-cell receptor gamma-chain genes. This pattern of lineage-related gene expression appears to define a distinct subtype of AML with T-lymphoid features (CD2+ AML) and could reflect either aberrant gene expression in leukemic blasts or transformation of a pluripotent stem cell having a flexible pattern of gene expression. Clinically, these 10 patients presented at an older age with a higher leukocyte count and a higher frequency of lymphadenopathy than did children whose blast cells were characteristic of myeloid leukemia. Patients with CD2+ AML also had poorer responses to remission induction therapy (50% v 80% entered complete remission, P = .05). However, each of the five children who failed induction chemotherapy on AML protocols had a striking response to drug combinations usually reserved for lymphoid leukemia. We conclude that this leukemia with mixed lymphoid and myeloid characteristics is a distinct biologic and clinical entity.

Adolescent↗

PubMed1988

Cytogenetics of childhood T-cell leukemia.

The karyotypes of 57 cases of childhood T-cell acute lymphoblastic leukemia (ALL) were analyzed to establish the cytogenetic profile in this disease. Three questions were of particular interest. Do the chromosomal changes in T-cell ALL preferentially affect bands where genes encoding the T-cell receptor for antigen (TCR) have been mapped? Do alterations involving the TCR gene regions appear with any notable frequency in B-progenitor ALL? Do chromosomal abnormalities in this disease relate to stage of T-cell ontogeny? A relatively high proportion of cases (65%) had a pseudodiploid karyotype at presentation, the majority (58%) characterized by a translocation. The overall frequency of translocations was 44%, comparable to that among all banded cases of ALL seen in our laboratory. Hypodiploidy and hyperdiploidy were exceedingly rare (only four of 57 cases); 16 cases (28%) had apparently normal karyotypes. In half the cases with a translocation (14 of 24), the breakpoints were in regions to which the alpha and beta chain TCR genes have been mapped. Chromosomal breakpoints that were consistently observed in the vicinity of TCR gene loci were 7q32-q36 (TCR beta chain; n = 8), 14q11-q13 (TCR alpha chain; n = 6); other frequent breakpoints were 9p13-pter (n = 8) and 6q15-qter (n = 9). Chromosomal alterations occurred near TCR gene loci significantly more often in T-cell cases than in a comparison group of 335 patients with B-cell precursor ALL (26% v 1.5%, P = .0001). Stage I thymocyte development (CD7+, CD2+, CD5+, CD1-, CD3-, CD4-, CD8-) was noted in 23 cases, stage II (CD7+, CD2+, CD5+, CD1+, CD3-, CD4 +/-, CD8 +/-) in 25 cases, and stage III (CD9+, CD2+, CD1-, CD5+, CD3+, and either CD4+ or CD8+) in nine cases. The only statistically significant associations between cytogenetic findings and T-cell ontogeny were a higher frequency of normal karyotypes in cases with stage I thymocytes, and of pseudodiploidy in stage II cases. There was no apparent relationship between particular translocations and level of thymocyte maturation. Our findings indicate that most children with T-cell ALL have pseudodiploid karyotypes, although a surprisingly high percentage lack demonstrable abnormal clones. Specific chromosomal changes do not appear to be related to discrete stages of T-cell ontogeny as defined in this study, but they occur preferentially in bands containing TCR genes.

Cell Differentiation↗

PubMed1987

Cytogenetic and molecular genetic studies of a patient with atypical lymphoid hyperplasia.

We have karyotyped cells from a lymph node of a patient with atypical lymphoid hyperplasia. Among other clonal chromosomal abnormalities, a t(2;19) translocation was observed with breakpoints at 2p11.2 and 19q13. The genes for transforming growth factor alpha and beta have been mapped to 2p11-p13 and 19q13, respectively, but Southern blot analysis did not reveal any alteration in the structure of these genes. Similarly, the kappa immunoglobulin gene, which maps to 2p11-p12 was not rearranged. In addition, Southern blot analysis using immunoglobulin and T-cell receptor genes as probes, did not demonstrate any clonality of either B or T cells. We propose that this patient represents an early, polyclonal stage of atypical hyperplasia. The chromosome changes observed may have been one of the etiologic factors causing this disorder.

Aged↗

PubMed1987

Provocative pattern of rearrangements of the genes for the gamma and beta chains of the T-cell receptor in human leukemias.

To examine the distribution of rearrangements of the gamma- and beta-chain T-cell receptor (TCR) genes in T- and non-T acute lymphoblastic leukemias (ALLs), and potentially to determine which genes rearrange first in ontogeny, we analyzed high molecular weight DNA from 102 patients with acute leukemia. Rearranged gamma- and beta-chain genes were found in all T-cell ALLs (22/22) examined. Overall, 27% (18/66) of B-lineage ALLs had beta-chain gene rearrangements, and 41% (24/58) had gamma-chain gene rearrangements, but the distribution of rearranged genes varied according to the stage of B-cell differentiation. The gamma-chain genes were rearranged in 11% (1/9) of the B-lineage patients negative for the common acute lymphoblastic leukemia antigen (cALLA) and 50% (23/46) of cALLA+ ALL patients, while the beta-chain genes were not rearranged in any of the 7 cALLA- ALL patients examined but were rearranged in 32% (18/56) of the cALLA+ patients. Neither TCR gene was found to be rearranged in acute nonlymphoid leukemia patients (0/12) or in patients with B-cell (surface immunoglobulin-positive) leukemia (0/3). Of the 44 cALLA+ patients in which a direct comparison of gamma- and beta-chain gene rearrangements could be made, 34% had both genes rearranged, 16% had only gamma-chain gene rearrangements, and the remaining 50% had both genes in the germ-line configuration. beta-Chain rearrangements have not been found in the absence of gamma-chain rearrangements, thus supporting a proposed hierarchy of TCR gene rearrangements. A provocative finding was that only a small percentage (11%) of the patients with cALLA- B precursor cell ALLs had rearranged TCR genes, while 50% of the cALLA+ leukemia patients had at least gamma-chain rearrangement, raising a question as to whether indeed cALLA- cells are precursors to cALLA+ cells. Interestingly, 18% (2/11) of the cytoplasmic immunoglobulin (cIg)-positive cALLA+ (pre-B) ALLs involved TCR gene rearrangements, compared to 60% (21/35) of the cIg-negative cases, suggesting the possibility that the majority of functional B cells are derived from the cALLA+ pool that contains immunoglobulin but not TCR gene rearrangements.

Adolescent↗

PubMed1987

Clinical significance of low levels of myeloperoxidase positivity in childhood acute nonlymphoblastic leukemia.

The clinical significance of a low percentage of myeloperoxidase-positive blast cells in childhood acute nonlymphoblastic leukemia was determined. Of 155 consecutive cases studied by cytochemical staining methods, 14 were characterized by 4% to 15% (median 6%) myeloperoxidase-positive blasts. All 14 cases showed reactivity to Sudan black B stain, and 7 had Auer rods. The morphological subtypes of leukemia were M1 (8 cases), M2 (3), M4 (1), and M5 (2). Immunological marker studies disclosed the lymphoid-associated T11 antigen on cells from 8 of the 11 cases tested. Other lymphoid-related findings in these 8 cases included the T3 antigen and E rosette formation in 1 case each. Among cases that were prospectively studied for the expression of lymphoid-associated markers, 6 of 8 with low levels of myeloperoxidase positivity compared with only 1 of 44 with higher levels (greater than 15%) possessed such features (P less than 0.001). We conclude that low levels of myeloperoxidase reactivity distinguish cases of acute leukemia in which the blast cells coexpress lymphoid (T11 antigen) and myeloid markers.

Acute Disease↗

PubMed1987

T cell differentiation stages identified by molecular and immunologic analysis of the T cell receptor complex in childhood lymphoblastic leukemia.

T cell differentiation was investigated by determining the relationship of T cell receptor (Ti) gene rearrangement and transcription to the expression of surface and cytoplasmic T3 antigen using blast cells from five children with acute lymphoblastic leukemia of thymic origin. Patterns of monoclonal antibody (MoAb) reactivity indicated that these cases were representative of the three recognized stages (I, II, III) of human thymocyte development. The T3 antigen, which becomes linked to the Ti to form a functional T cell receptor complex on mature thymocytes, was expressed on the cell surface in two cases (stage III). However, in the remaining three cases that were surface T3 negative (stages I and II), large amounts of T3 were identified in the cytoplasm by immunoperoxidase staining and flow cytometry. Leukemic blasts from all five patients showed rearranged genes encoding the beta-chain portion of the Ti heterodimer. RNA transcripts of Ti beta-chain genes were also evident in lymphoblasts from all five cases, but transcripts coding for the alpha-chain portion of Ti were found only in cases that expressed T3 on the cell surface. Thus the absence of surface T3 (and presumably Ti) coincides with the absence of Ti alpha-chain RNA, suggesting that transcription of alpha-chain genes is a critical regulatory event in the surface expression of the Ti-T3 complex. Leukemic T cells that rearrange and express Ti beta-chain genes but lack Ti alpha-chain messenger RNA (mRNA) may represent a stage of differentiation analogous to pre-B cells, where heavy-chain immunoglobulin (Ig) genes are rearranged and expressed but light-chain Ig genes are not expressed.

Antibodies, Monoclonal↗