scholarly journals A rare morphological and immunophenotypic presentation of adult B-cell acute lymphoblastic leukemia with blasts in the monocytic zone on CD45 side scatter

2019 ◽  
Vol 5 (3) ◽  
pp. 82
Author(s):  
Shuaeb Bhat ◽  
Saleem Hussain
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Bone Marrow Aspirate ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Flow Cytometric Analysis ◽  
Blood Film ◽  
High Side

<p class="abstract">We present a case of B-acute lymphoblastic leukemia in an elderly patient who presented with severe weakness and pancytopenia. The patient was a 75 year old Female whose blasts had an unusual morphology in form of coarse azurophilic granules and cytoplasmic blebs and on flow cytometry the blasts were present in the bright CD45 zone with a high side scatter. Bone marrow aspirate sample was subjected to multicolour flow cytometry using Beckman Coulter Navios® which is an 8 colour flow cytometer.  Flow cytometric analysis of the bone marrow aspirate showed blasts in the monocytic zone with a precursor B cell immunophenotype. Complete blood counts showed pancytopenia with peripheral blood film not showing any blasts. Bone marrow aspirate smears showed 20% blasts with coarse azurophilic granules and cytoplasmic blebs. The position of the blasts in this case which were in monocytic zone giving them a bright expression of CD45 and a high side scatter on the CD45 side scatter. This is not the usual position for blasts in B- acute lymphoblastic leukemia as these blasts are less complex. A bright expression of CD45 by blasts in B- acute lymphoblastic leukemia is known to be associated with a poor prognosis but the clinical significance of blasts being bright CD45 with a high side scatter is a very rare occurrence and more number of cases with a similar presentation are required to determine a prognostic significance.</p>

Successful Treatment of Refractory Acute Lymphoblastic Leukemia with Tisagenlecleucel in the Setting of Life-Threatening Infection

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5125-5125
Author(s):  
Keith J August ◽  
Terrie Flatt ◽  
Erin Marie Hall ◽  
Doug Myers
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Bone Marrow Aspirate ◽  
Lymphoblastic Leukemia ◽  
Severe Neutropenia ◽  
Active Infection ◽  
Post Infusion ◽  
Life Threatening ◽  
Cell Acute Lymphoblastic Leukemia

Tisagenlecleucel is a CD19 directed immunotherapy approved for the treatment of young patients with relapsed or refractory precursor B-cell acute lymphoblastic leukemia (ALL). The most important toxicity related to tisagenlecleucel therapy is cytokine release syndrome (CRS). CRS is an exaggerated systemic inflammatory response that occurs frequently along with T-cell expansion following the administration of tisagenlecleucel. Tisagenlecleucel guidelines recommend delaying treatment when an active infection is present due to the concern that the pre-existing inflammatory response associated with infection may predispose patients to severe CRS. We describe two cases where tisagenlecleucel was successfully administered to patients in the setting of life-threatening infection. Patient 1 is a 23-year-old Caucasian male with refractory Philadelphia chromosome negative B-cell ALL who had received prior treatment with chemotherapy, blinatumomab, inotuzumab ozogamicin and a haploidentical stem cell transplant (SCT) followed by multiple Zalmoxis infusions. Five months following SCT he relapsed. At relapse, he underwent leukapheresis followed by bridging chemotherapy with ifosfamide and etoposide. He developed severe neutropenia and respiratory failure associated with a right lower lung consolidation. A biopsy demonstrated a mucormycosis infection and he required surgical debridement including resection of portions of the lung, diaphragm and liver. At this time, he had 92% blasts in the bone marrow. Eleven days after his surgery he received tisagenlecleucel despite being persistently febrile. Prior to the infusion, he received a modified lymphodepleting chemotherapy regimen including two days of fludarabine and cytarabine. Due to severe neutropenia, he was receiving granulocyte transfusions. These were discontinued prior to the infusion and resumed after 12 days. CRP and ferritin the day prior to infusion were 26.2 mg/dL and 18,419 ng/mL. He remained persistently febrile for 13 days post-infusion. He received a single dose of tociluzimab 7 days following his infusion due to high fevers. He did not require any treatment with corticosteroids for CRS. The absolute neutrophil count recovered to >500x103/µL at 31 days post infusion. A bone marrow aspirate done 26 days post-infusion did not show any evidence of leukemia by multicolor flow cytometry (MFC). He remains alive without evidence of disease 11 months after treatment with tisagenlecleucel. Patient 2 is a 4-year-old Hispanic female with refractory B-cell ALL found to have a TP53 deletion and t(1;19). She had received prior treatment with chemotherapy, blinatumomab and local radiation therapy to the site of extramedullary disease found in the left maxillary sinus at relapse. She underwent leukapheresis and received bridging chemotherapy with mercaptopurine and methotrexate. After 3 days of lymphodepleting chemotherapy she developed septic shock and E. Coli bacteremia. She became severely ill requiring continuous renal replacement therapy for 5 days and extracorporeal membrane oxygenation (ECMO) for 6 days. Shortly after ECMO decannulation she developed fever and was found to have multiple pulmonary opacities concerning for fungal infection. Blasts were noted in the peripheral blood. Sixteen days after presenting with septic shock and 11 days from ECMO she received tisagenlecleucel. CRP at the time of infusion was 22.9 mg/dL. She developed persistent fevers post-infusion for 17 days. She received two doses of tociluzimab 20- and 21-days post-infusion due to recurrence of high fever and reactive lymphadenopathy with third spacing and concern for renovascular compromise. She did not require any treatment with corticosteroids for CRS. Bone marrow aspirate done 32 days post-infusion did not show any evidence of leukemia by MFC. The absolute neutrophil count recovered to >500x103/µL at 59 days post infusion. The patient remained without evidence of disease for 7 months following treatment but died due to infectious complications with persistent pancytopenia. Tisagenlecleucel is a potentially life-saving treatment for relapsed and refractory B-cell acute lymphoblastic leukemia in children and young adults 24 years of age or younger. Tisagenlecleucel is an option for the treatment of patients with active infection and/or inflammation with progressive leukemia when no other therapeutic alternative exists. Disclosures August: Novartis Pharmaceuticals: Speakers Bureau. Myers:Novartis Pharmaceuticals: Consultancy, Speakers Bureau.

CD20 up-Regulation In Induction Therapy for Childhood B Lymphoblastic Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2124-2124 ◽  
Author(s):  
Tanya C. Watt ◽  
Sunita Park ◽  
Todd Cooper
Keyword(s):  
Monoclonal Antibody ◽  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
Prognostic Significance ◽  
Cell Precursor ◽  
Cd20 Expression ◽  
Anti Cd20

Abstract Abstract 2124 Background: Despite improvement in survival rates for B lymphoblastic leukemia (B-ALL), children who relapse have dismal outcomes. Antibody-directed therapies represent a novel strategy to improve survival rates. Approximately 50% of children diagnosed with B-ALL express CD20 on the blast surface, providing a potential therapeutic target.1 A recent study in Europe suggested one week pretreatment with corticosteroids resulted in an increase in CD20 expression, even in samples that were initially CD20 negative.2 This increased expression potentiated cytotoxicity by rituximab, an anti-CD20 monoclonal antibody. Demonstration of CD20 up-regulation on lymphoblasts in children treated with combination cytotoxic chemotherapy and corticosteroids would provide an important rationale for the inclusion of CD20 monoclonal antibody therapy in childhood B-ALL. Methods: A retrospective review was performed on 84 consecutive children diagnosed with B-ALL between June 2008 and March 2010 at Children's Healthcare of Atlanta. Flow cytometry records were reviewed for expression of CD20 on the surface of leukemic blasts at various time points during induction (day 1, 8, 15, and 29). Samples were considered positive for CD20 if greater than 20% of blasts expressed the antigen. To quantify the exact percentage of CD20 expression, lymphoblasts were gated on the CD19 surface antigen, and the percentage of blasts with surface CD20 was recorded. The Wilcoxon signed-rank test (2-tailed) was used to assess the significance of the differences between data in paired samples. Comparisons between the following paired bone marrow samples were performed: day 1 and 8, day 1 and 15, day 1 and 29, day 8 and 15, and day 15 and 29. For each analysis, only samples with both data points were included. Results: Sixty-eight percent of patients had positive CD20 expression on the diagnostic bone marrow specimen. At day 8, 22% of the initially negative samples expressed CD20. As demonstrated in Table, the mean percentage of lymphoblasts that expressed CD20 increased from day 1 through the remainder of therapy. The difference in the percentage of blasts that expressed CD20 between days 1 and 8 and days 1 and 15 was statistically significant. Comparisons between other days were limited by a small sample size, obviating any difference in the data. There was no difference in up-regulation between patients treated with dexamethasone or prednisone during induction. Conclusions: Adult studies suggest that CD20 expression in B-ALL confers a worse prognosis. 3 A recent clinical trial demonstrated an improved 3 year EFS (68 vs. 28%, p<0.001) in CD20 positive B-ALL adults with the addition of rituximab.4 In vitro work by Dworzak et al suggests one week of corticosteroid monotherapy increases CD20 expression, leading to increased rituximab cytotoxicity.2 Our data demonstrates statistically significant up-regulation in children, even in the setting of multi-agent chemotherapy such as that used in pediatric clinical trials. This data provides rationale for the addition of CD20 monoclonal antibodies to induction therapy in childhood B-ALL. References: 1. Jeha S, Behm F, Pei D, et al. Prognostic significance of CD20 expression in childhood B-cell precursor acute lymphoblastic leukemia. Blood 2006;108:3302-4. 2. Dworzak MN, Schumich A, Printz D, et al. CD20 up-regulation in pediatric B-cell precursor acute lymphoblastic leukemia during induction treatment: setting the stage for anti-CD20 directed immunotherapy. Blood 2008;112:3982-8. 3. Thomas DA, O'Brien S, Jorgensen JL, et al. Prognostic significance of CD20 expression in adults with de novo precursor B-lineage acute lymphoblastic leukemia. Blood 2008. 4. Thomas D CJ, et al. Update of the modified hyper-CVAD regimen with or without rituximab in newly diagnosed adult acute lymphoblastic leukemia (ALL). ASH Abstract 2008. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Expression of Blood Coagulation Factor Xiiia in Lymphoblasts Predicts Favorable Outcome in Childhood B-Cell Precursor Acute Lymphoblastic Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5283-5283
Author(s):  
Csongor Kiss ◽  
Bettina Kárai ◽  
Zsuzsanna Hevessy ◽  
Eszter Szánthó ◽  
László Csáthy ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Factor Xiii ◽  
Lymphoblastic Leukemia ◽  
Coagulation Factor ◽  
Cell Precursor ◽  
Expression Site

Abstract Introduction: Previously we identified B-cell lineage leukemic lymphoblasts as a new expression site for subunit A of blood coagulation factor XIII (FXIIIA)1. On the basis of FXIIIA expression, various subgroups of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) can be identified. Methods. Fifty-five children with BCP-ALL treated within the frame of BFM ALL-IC 2002 clinical trial were studied retrospectively. Bone marrow samples were obtained by aspiration and the expression of FXIIIA was detected by flow cytometry. G-banding and fluorescent in situ hybridization was performed according to standard procedures. Results. The 10-year event-free survival (EFS) and overall survival (OS) rate of FXIIIA-positive and FXIIIA-negative patients showed significant differences (EFS: 84% vs. 61%, respectively; p=0.031; OS: 89% vs. 61%; p=0.008). Of all the parameters examined, the only correlation was between the lack of FXIIIA expression and 'B-other' genetic subgroup. Further multivariate Cox regression analysis of FXIII-subtype and genetic group or 'B-other' subgroup identified FXIIIA-negative characteristics as an independent predictor for poor outcome in BCP-ALL. Conclusion. We found an excellent correlation between long-term survival and FXIIIA-positive phenotype of lymphoblasts in de novo childhood BCP-ALL. The results presented seem to be convincing enough to suggest a possible role for FXIIIA expression in the prognostic grouping of childhood BCP-ALL patients. In addition, lack of FXIIIA expression is associated with the 'B-other' characteristics, therefore, FXIIIA can help to identify those cases that may require further detailed genetic examination by using expensive methods. Acknowledgment. The authors thank Dr. Erzsebet Balogh for performing the cytogenetic analyses and Csaba Antal for his administrative help. The authors are grateful to Dr. Kalman Nagy and their coworkers at the Borsod-Abaúj-Zemplén County Hospital and University Hospital for sending bone marrow samples for flow cytometry. This study was supported by grant OTKA K-108885 (CK). Authors declare no conflict of interest. References. 1. Kiss F, Hevessy Z, Veszpremi A, Katona E, Kiss C, Vereb G, Muszbek L, Kappelmayer JN. Leukemic lymphoblasts, a novel expression site of coagulation factor XIII subunit A. Thromb Haemost. 2006; 96: 176-82. Legend to figures. Figure 1. Prognostic value of FXIII-A expression of lymphoblasts in children with B-cell precursor ALLKaplan Meier plots of event-free (A) and overall survival (B) showed significant difference between the FXIIIA-positive and FXIII-A-negative groups (p=0.031 and p=0.008). Figure 2. Relationship between FXIIIA expression profile and genetic classification The distribution of patients in the various genetic groups differed significantly in terms of FXIII-A profile using Chi square test. Recurrent genetic abnormalities: BCR-ABL1, KMT2A (MLL) gene rearrangements, ETV6-RUNX1 (TEL-AML1), E2A/PBX1 and high hyperdiploidy. Disclosures No relevant conflicts of interest to declare.

scholarly journals Co-culture model of B-cell acute lymphoblastic leukemia recapitulates a transcription signature of chemotherapy-refractory minimal residual disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Stephanie L. Rellick ◽  
Gangqing Hu ◽  
Debra Piktel ◽  
Karen H. Martin ◽  
Werner J. Geldenhuys ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Tumor Cells ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Adherent Cells ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Minimal Residual

AbstractB-cell acute lymphoblastic leukemia (ALL) is characterized by accumulation of immature hematopoietic cells in the bone marrow, a well-established sanctuary site for leukemic cell survival during treatment. While standard of care treatment results in remission in most patients, a small population of patients will relapse, due to the presence of minimal residual disease (MRD) consisting of dormant, chemotherapy-resistant tumor cells. To interrogate this clinically relevant population of treatment refractory cells, we developed an in vitro cell model in which human ALL cells are grown in co-culture with human derived bone marrow stromal cells or osteoblasts. Within this co-culture, tumor cells are found in suspension, lightly attached to the top of the adherent cells, or buried under the adherent cells in a population that is phase dim (PD) by light microscopy. PD cells are dormant and chemotherapy-resistant, consistent with the population of cells that underlies MRD. In the current study, we characterized the transcriptional signature of PD cells by RNA-Seq, and these data were compared to a published expression data set derived from human MRD B-cell ALL patients. Our comparative analyses revealed that the PD cell population is markedly similar to the MRD expression patterns from the primary cells isolated from patients. We further identified genes and key signaling pathways that are common between the PD tumor cells from co-culture and patient derived MRD cells as potential therapeutic targets for future studies.

scholarly journals High cortactin expression in B-cell acute lymphoblastic leukemia is associated with increased transendothelial migration and bone marrow relapse

Leukemia ◽  
2018 ◽  
Vol 33 (6) ◽  
pp. 1337-1348 ◽  
Author(s):  
Martha Velázquez-Avila ◽  
Juan Carlos Balandrán ◽  
Dalia Ramírez-Ramírez ◽  
Mirella Velázquez-Avila ◽  
Antonio Sandoval ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Transendothelial Migration ◽  
Cell Acute Lymphoblastic Leukemia

scholarly journals The influence of a dosage regimen of dexamethasone on detection of normal B-cell precursors in the bone marrow of children with BCP-ALL at the end of induction therapy

2020 ◽  
Vol 19 (1) ◽  
pp. 53-57
Author(s):  
E. V. Mikhailova ◽  
T. Yu. Verzhbitskaya ◽  
J. V. Roumiantseva ◽  
O. I. Illarionova ◽  
A. A. Semchenkova ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
B Cell ◽  
Induction Therapy ◽  
Therapy Group ◽  
Lymphoblastic Leukemia ◽  
Leukemic Cells ◽  
Intermittent Therapy ◽  
Continuous Therapy ◽  
B Cell Precursors

Minimal residual disease (MRD) monitoring by flow cytometry at the end of induction therapy is one of the key ways of a prognosis assessment in patients with acute lymphoblastic leukemia (ALL). In B-cell precursor ALL (BCP–ALL), this method of MRD detection is complicated due to the immunophenotypic similarity between leukemic cells and normal B-cell precursors (BCPs). A decrease in intensity of induction therapy can lead to a more frequent appearance of normal BCPs in the bone marrow, which significantly complicates the MRD monitoring. Aim: to assess the incidence of normal BCPs in bone marrow on the 36th day of induction therapy with two different regimens of glucocorticoid (GC) administration according to ALL-MB 2015 protocol. This study was approved by the Independent Ethical Committee and the Academic Council of Dmitriy Rogachev National Medical Research Center of Pediatric Hematology, Oncology, Immunology Ministry of Healthcare of Russian Federation. The study included 220 patients with BCP-ALL who were randomized to two types of GC-based induction therapy: a continuous administration of dexamethasone (n = 139) and an intermittent regimen with a 1-week dexamethasone therapy stop (n = 81). On the 36th day of induction therapy, MRD and normal BCPs were quantified in bone marrow samples by flow cytometry. On the 36th day of treatment, 43.2% of BCP(+) samples were established in the intermittent-therapy group, and 27.3% in the continuous-therapy group (p = 0.016). Comparison of the BCP level in BCP(+) samples revealed the more equitable distribution of BCPs at different developmental stages in the intermittent-therapy group, meanwhile mainly the immature BCPs in a quantity of less than 0.01% were found in the continuous-therapy group. Reduced-intensity induction therapy for patients with BCP-ALL leads to a noticeable increase of normal BCPs in bone marrow at the end of this treatment stage. A higher rate of BCP(+) bone marrow samples hinder the MRD detection due to the immunophenotypic similarity of BCPs and leukemic cells.

scholarly journals Interleukin-4 induces programmed cell death (apoptosis) in cases of high-risk acute lymphoblastic leukemia

Blood ◽  
1994 ◽  
Vol 83 (7) ◽  
pp. 1731-1737 ◽  
Author(s):  
A Manabe ◽  
E Coustan-Smith ◽  
M Kumagai ◽  
FG Behm ◽  
SC Raimondi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Death ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Programmed Cell Death ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Fatal Outcome ◽  
Interleukin 4 ◽  
B Lineage

Abstract We investigated the effects of interleukin-4 (IL-4) on the survival of leukemic and normal B-cell progenitors cultured on bone marrow stroma. IL-4 (at 100 U/mL) was cytotoxic in 16 of 21 cases of B-lineage acute lymphoblastic leukemia, causing reductions in CD19+ cell numbers that ranged from 50% to greater than 99% (median 83.5%) of those in parallel cultures not exposed to the cytokine. All nine cases with the t(9;22)(q34;q11) or the t(4;11)(q21;q23), chromosomal features that are often associated with multidrug resistance and a fatal outcome, were susceptible to IL-4 toxicity. IL-4 cytotoxicity resulted from induction of programmed cell death (apoptosis); there was no evidence of cell killing mediated by T, natural killer, or stromal cells. IL-4 cytotoxicity extended to a proportion of normal B-cell progenitors. After 7 days of culture with IL-4 at 100 U/mL, fewer CD19+, CD34+ normal lymphoblasts (the most immature subset) survived: in five experiments the mean (+/- SEM) reduction in cell recoveries caused by IL-4 was 60.0% +/- 6.0%. By contrast, reductions in recovery of more differentiated bone marrow B cells (CD19+, CD34-, surface Ig+) were low (6.6% +/- 2.2%; P < .001 by t-test). Our findings indicate that IL-4 is cytotoxic for human B-cell precursors and support clinical testing of IL-4 in cases of high-risk lymphoblastic leukemia resistant to conventional therapy.

scholarly journals TEL-AML1 Fusion Transcript in Relapsed Childhood Acute Lymphoblastic Leukemia

Blood ◽  
1998 ◽  
Vol 91 (5) ◽  
pp. 1716-1722 ◽  
Author(s):  
Karlheinz Seeger ◽  
Hans-Peter Adams ◽  
Dirk Buchwald ◽  
Birgit Beyermann ◽  
Bernhard Kremens ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Philadelphia Chromosome ◽  
Fusion Transcript ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Long Term Results ◽  
Childhood All ◽  
Cryptic Translocation

Abstract The cryptic translocation t(12;21)(p13;q22) has been recently recognized as the most common genetic rearrangement in B-lineage childhood acute lymphoblastic leukemia (ALL). The resulting fusion transcript, termed TEL-AML1, has been associated with an excellent prognosis at initial ALL diagnosis. Hence, we postulated that the incidence of TEL-AML1 fusion should be lower in patients with ALL relapse. To address this assumption and to investigate the prognostic significance of TEL-AML1 expression in relapsed childhood ALL, bone marrow samples of 146 children were analyzed by reverse-transcriptase (RT)-polymerase chain reaction (PCR). All children were treated according to Berlin-Frankfurt-Münster (BFM) ALL relapse trial protocols (ALL-REZ BFM 90-96). Their clinical features and outcome were compared with those of 262 patients who could not be tested due to lack of bone marrow samples. Thirty-two of 146 children with relapsed ALL were TEL-AML1–positive. Four of the negative patients had T-lineage and nine Philadelphia chromosome (Ph1)-positive leukemia. Thus, the incidence ofTEL-AML1 in relapsed Ph1-negative, B-cell precursor ALL is 32 of 133 (24%). The 32 TEL-AML1–positive and 101 negative patients differed significantly with respect to duration of last remission (42.5 v 27 months; P = .0001) and age at initial diagnosis (53.5 v 74 months;P = .0269). At a median follow-up time of 21.5 months, children positive for TEL-AML1 had a significantly (P = .0011) higher probability of event-free survival (EFS; 0.79 v 0.33). The predominant majority of patients had been treated for initial ALL according to German multicenter BFM (108 of 133) or Cooperative ALL study group (CoALL) (19 of 133) frontline protocols. The comparison of tested and not-tested (N = 262) patients showed no significant difference.TEL-AML1 positivity predicted a favorable short-term outcome; long-term results are unknown. Screening for TEL-AML1 should become routine at relapse diagnosis and might be used for therapy stratification in future trials.

scholarly journals Clinical and laboratory characteristics of acute leukemia with the 4;11 translocation

Blood ◽  
1986 ◽  
Vol 67 (3) ◽  
pp. 689-697 ◽  
Author(s):  
J Mirro ◽  
G Kitchingman ◽  
D Williams ◽  
GJ Lauzon ◽  
CC Lin ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Acute Leukemia ◽  
B Cell ◽  
Heavy Chain ◽  
Gene Rearrangement ◽  
Lymphoblastic Leukemia ◽  
Flow Cytometric Analysis ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Immunoglobulin Gene ◽  
Immunoglobulin Gene Rearrangement

Abstract This report describes the clinical and laboratory features of seven cases of acute leukemia associated with the 4;11 chromosomal translocation. All seven children had acute lymphoblastic leukemia by standard morphologic and cytochemical criteria. Leukemic blasts from six of seven patients were terminal deoxynucleotidyl transferase- positive. Immunologic phenotyping suggested the leukemias were of B cell origin; blasts from five patients expressed HLA-DR and p24 (CD-9 antibody), blasts from three patients expressed B4 (CD-19), and blasts from two patients expressed the common acute lymphoblastic leukemia antigen (CD-10). One patient's leukemic blasts contained cytoplasmic immunoglobulin. Analysis of DNA from four of five patients demonstrated additional evidence of B cell differentiation with heavy-chain immunoglobulin gene rearrangement. When DNA from the four patients with heavy-chain immunoglobulin gene rearrangement was analyzed, one patient's DNA demonstrated light-chain immunoglobulin gene rearrangement. However, flow cytometric analysis of blasts from three patients showed the simultaneous expression of the lymphoid-associated antigen B4 (CD-19) and the myeloid-associated antigen My-1 (X-Hapten). Electron microscopic examination of blasts from one patient that expressed both lymphoid- and myeloid-associated antigens demonstrated ultrastructural characteristics of both lineages. These findings suggest that acute leukemia with the t(4;11) abnormality has mixed lineage characteristics as a result of leukemogenesis in a multipotential progenitor cell or aberrant gene expression later in differentiation. Furthermore, serial analysis of karyotype, immunophenotype, and heavy-chain immunoglobulin genes revealed changes in these biologic markers over time, suggesting continued chromosome rearrangement and gene modulation after the leukemogenic event in cells with the t(4;11).

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