BRIEF REPORTAcute Lymphoblastic Leukemia of Burkitt Type (L3 ALL) With t(8;14) Lacking

Surface and Cytoplasmic Immunoglobulins

Chaim Kaplinsky* and Gideon Rechavi

Key words: non-Hodgkin lymphoma; paraspinal mass; immunoglobulin generearrangement

We present a unique patient with FAB L3 acute lym-phoblastic leukemia with t(8;14) translocation lackingboth surface (sIg) and cytoplasmic immunoglobulins anddiscuss the significance of these findings.

A 6-year-old Arab boy from Gaza was referred to ourPediatric Hemato-Oncology Department in December1993 for evaluation and further treatment because ofparaspinal masses at the T7–T8 level and paraplegia. Thehistopathology of the extradural mass was compatiblewith non-Hodgkin lymphoma of the Burkitt type. Bonemarrow aspiration showed a normal-to-hypercellularmarrow without blasts. Cerebrospinal fluid displayedpleocytosis with L3-lymphoblasts, reacting positivelywith CD45-90%, CD34-20%, CD20-40%, CD19-30%.No surface or cytoplasmic immunoglobulins (cIg) weredetected.

In November 1995, he relapsed in bone marrow andCNS. Immunophenotyping of reactivity was with CD20-78%, CD19-83%, CD10-85%, and HLA-DR-74%. Nosurface and cytoplasmic immunoglobulin Gamma, mu,Kappa, and Lambda chains were detected. Terminal de-oxynucleotide transferase was negative. Ig genes and T-cell receptor B-chain gene were in germline configura-tion (Figs. 1,2). Cytogenetic studies showed t(8;14)(q24;q32) int del (2) (q14;q31), in about 50% of meta-phases (Fig. 3).

This patient exhibits unique clinical and laboratoryfeatures of BL/B-ALL with L3 morphological appear-ance, B-cell immunophenotype, immunoglobulin genesin germline configuration, t(8;14) translocation, and nosurface or intracytoplasmic immunoglobulins. The longinterval prior to the recurrence of disease is also remark-able compared to the early relapse so typical of Burkittlymphoma and B-ALL.

Several reports cite acute lymphoblastic leukemiawith Burkitt cell morphology lacking surface immuno-globulin but containing cytoplasmic mu [1–4]. One casedescribes both surface and intracytoplasmic immuno-globulins but with a normal karyotype [5]. Two cases

report clonal evolution from pre-B to B-ALL lackingsurface immunoglobulins prior to conversion, but ex-pressing both IgG and K when morphologically subtypedas L3 [6].

Several explanations may be offered for this uniqueBL characterized by lack of immunoglobulin gene rear-rangement and expression. First, the transforming event,t(8;14) translocation, may have occurred at the very earlystage of B-cell differentiation before an Ig gene rear-rangement could occur [7]. Second, the high reactivity toCD10 and the absence of expression of TdT and surfaceIgM and Ig genes in germ line point to a deregulated (ordiscordant) developmental B-cell ontogeny.

Normally, lymphoid cells undergo a precise programof genetic rearrangement; however, these specific lociare subject to recombination errors, the results of whichinclude chromosomal translocations. Although transloca-tions occur very early in lymphoid ontogeny, tumor phe-notype and morphology may be more differentiated.

Recent data demonstrate hypervariable mutations inBL and indicate, along with CD77 and CD10 expression,that they are phenotypically the neoplastic equivalent oflarge B-cell germinal follicle cells in most cases, ratherthan resting B cells. However, the translocation probablyoccurs early in differentiation. The question remains as towhy the cells undergo differentiation. One reason mightbe that they can more readly acquire mutations in, forexample, c-myc. Our data concerning this particular pa-tient support this possibility, i.e., the tumor was perhaps

Pediatric Hemato-Oncology Department, Institute of Hematology, TheChaim Sheba Medical Center, Tel Hashomer, Israel

*Correspondence to: Chaim Kaplinsky, Pediatric Hemato-OncologyDepartment, The Chaim Sheba Medical Center, Tel Hashomer 52621,Israel.

Received 22 July 1997; Accepted 8 February 1998

Medical and Pediatric Oncology 31:36–38 (1998)

© 1998 Wiley-Liss, Inc.

able to acquire additional mutations to enable it to avoidproliferation and differentiation checkpoints [8].

ACKNOWLEDGMENTS

We are indebted to Dr. Magrath for his critical reviewand comments, and for his instructive ideas.

REFERENCES

1. Stevens DA, O’Connor GT, Levine PH, et al.: Leukemia with“Burkitt’s lymphoma cells” and Burkitt’s lymphoma. Ann InternMed 76:967–973, 1972.

2. Flandrin G, Brouet JC, Daniel MT, et al.: Acute leukemia withBurkitt’s tumor cells. Blood 45:183–188, 1975.

3. Ganick DJ, Finlay JL: Acute lymphoblastic leukemia with Burkitt

Fig. 1. Southern blot analysis of the immunoglobulin heavy chainJH. Lane 1: Control DNA exhibits germline configuration.Lane 2:Tumor DNA in which no rearrangement was detected. DNA was di-gested by the Hind III restriction endonuclease. The radiolabeled probewas the 6-kb JH fragment (Oncor).

Fig. 2. Southern blot analysis of the T-cell receptor beta chain.Lane1: Control DNA in germline configuration.Lane 2: Tumoral DNA ingermline; no rearrangement was detected. The radiolabeled probe wasa 420-bp T beta fragment.

Fig. 3. A partial karyotype showing the t(8;14)(q24;q32) int del (2) (q14;q31).

L3 ALL Without sIg and cIg 37

cell morphology and cytoplasmic immunoglobulin. Blood56:311–314, 1980.

4. Gluck WL, Binger SH, Borowitz MJ, et al.: Acute lymphoblasticleukemia of Burkitt’s type (L3ALL) with 8:22 and 14:18 translo-cations and absent surface immunoglobulins. Am J Clin Pathol85:636–640, 1986.

5. Aso Y, Hirota Y, Matusmoto I, et al.: Acute lymphoblastic leu-kemia of Burkitt type (L3-ALL) without chromosome abnormal-ity and lacking surface and cytoplasmic immunoglobulins. Jpn JMedicine 28:632–635, 1989.

6. Toren A, Kende G, Mandel M, et al.: In vivo clonal evolution ofpre b- to b-cell acute lymphoblastic leukemia in childhood. Leu-kemia 8:1062–1064, 1994.

7. Haluska FG, Tsujimoto Y, Croce CM: The molecular genetics ofnon-Hodgkin’s lymphoma 1992. In Magrath, IT (ed): “The non-Hodgkin’s lymphoma.” 1978. Edward Arnold, pp. 96–108.

8. Melchers F, Haasner D, Grawunder U, et al.: Role of IgH and Lchains and of surrogate H and L chains in the development of cellsof the B lymphocyte lineage. Annu Rev Immunol 12:209–225,1994.

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