Acute leukemia with t(10;11)(p11-p15;q13-q23)

ELSEVIER

Acute Leukemia With t(lO;ll)(pll-pl5;ql3-q23) Christiane Secco, Peter H. Wiernik, John M. Bennett, and Elisabeth Paietta

ABSTRACT: We report six patients with acute leukemia characterized by the presence of a t(lo;ll) (pl l-p15;q13-q23), either as sole cytogenetic abnormality (three patients) or as part of a complex abnormal karyotype. The morphologic and cytochemical features of four patients were consistent with FAB-M5A, while two patients presented with FAB-Ll characteristics. By immunophenotyping, myeloid leukemia was (diagnosed in five patients, including one patient with FAB-Ll leukemia who typed as terminal transferase (TdT)‘, CD7 T-cell antigen’ acute myelomonocytic leukemia. Differentiated acute myeloid leukemia (AML) with expression of terminal transferase was found in two of the other cases and monocytic leukemia in two, with co-expression of T-cell antigens in one of them. The second FAB-Ll patient typed as undifferentiated acute lymphocytic leukemia (ALL) expressing myeloid antigens. Serial phenotypic studies in patient 3 during the course of the disease demonstrated a switch from monocytic to lymphoid morphology at the time of first and second relapse, which was paralleled by the appearance of a pre-T ALL immunophenotype with co-expression of the myeloid antigen CD33. These phenotypic changes occurred without apparent alteration in the genotype since t(lO;l l)(pll..2;qZ3) remained the only cytogenetic aberration at all stages of the disease. Our observations suggest that the (lO;ll) variant of 1 lq aberrations occurs in a bipotential myelomonocytic/T-lymphoid stem cell.

INTRODUCTION A number of nonrandom chromosome abnormalities have been previously described in acute leukemia, some of which are pathognomonic for certain disease subtypes [l, z]. For instance, the t(15;17) is uniquely associated with FAB-M3 morphologic and cytochemical features, as well as with the characteristic immunophenotype of acute promyelocytic leukemia, and is, therefore, diagnostic of this acute myeloid leukemia (AML) subtype [3]. Other cytogenetic aberrations may Ele associated with particular immunologic findings rather than a unique antigen profile, such as the t(8;21) in AML that typically lacks the CD2 T-cell antigen and expresses the B-cell marker CD19 [4, 51. Thirdly, specific cytogenetic abnormalities may occur in variable leukemia imm.unophenotypes, such as trisomy 8 [6], monosomy 7 (7, 81, or the Philadelphia chromosome, t(9;22) [8, 91, which is interpreted as reflecting a multipotent stem cell defect. Balanced or unbalanced translocations involving dele-

From the Department of Oncology, Montefiore and Albert Einstein Cancer Center, Bron.u, New York; Division of Medical Oncology, University of Rochester, Rochester, New York; and the Eastern Cooperative Oncology Group, Denver, Colorado. Address reprint requests to: Elisabeth Paietta, Ph.D., Montefiore Medical Center, Department of Oncology, 111 East 210th Street, Bronx, New York 10467. Received February 21, 1995; accepted

June 22, 1995.

Cancer Genet Cytogenet 86:31-34 (1996) 0 Elsevier Science Inc., 1996 655 Avenue of the Americas, New York, NY 10010

tions of the long arm of chromosome 11 in the “hot-spot” region q13-24 are associated with acute leukemias of differing biologic characteristics [l, 10, 111, although clinically llq aberrations are universally considered as a poor prognostic factor (111. A number of different chromosomes are involved in reciprocal translocations with llq, the most common being chromosome 9 in AML with monocytic characteristics and chromosome 4 in lymphoid/ monocytic acute leukemia. The t(lO;ll)(pll-p15;q13-q23) represents a rare variant of llq aberrations which has been detected in a variety of leukemia immunophenotypes, such as T-lymphoblastic leukemia [ 12, KS], acute monocytic leukemia (AMoL), or undifferentiated AML, as well as acute lymphocytic leukemia (ALL) [l&Ii’], irrespective of an apparent heterogeneity in the breakpoints on lop. We here describe six patients with t(lO;ll)(pll-15; ql3-q23). By FAB criteria, four patients were FAB-M5A and two were FAB-Ll. All but one patient presented with immunophenotypic features of both myeloid and lymphoid leukemia. Serial studies in one patient during the course of the disease demonstrated a switch in the morphology from monocytic to lymphoid and in the immunophenotype from AMoL to pre-T ALL without any change in the karyotype that persistently showed t(lO;ll) (p11.2;q23) as the sole cytogenetic abnormality in all metaphases examined. These observations support the notion that the t(lO;ll) occurs in a bipotential, myeloid/ T-lymphoid stem.

0165-4608/96/$15.00 SSDI 0165-4608(95)00165-L

C. Secco et al.

32 MATERIALS AND METHODS We studied six patients from August 1987 to November 1993. Four were enrolled in Eastern Cooperative Oncology Group (ECOG) protocols (E2993, E3489), as well as the ECOG laboratory protocol El485 which determines various biologic parameters such as immunophenotype and karyotype, and two patients were seen at Montefiore Medical Center. The age ranged from 18 to 59 years on presentation. There were three men and three women. Bone marrow samples were obtained on all six patients. The diagnosis of acute leukemia was based on the criteria of the French-American-British (FAB) classification system [18] and was confirmed by immunophenotyping for all patients in ECOG’s Immunophenotyping Reference Laboratory. Immunodiagnosis of AML and ALL subtypes were defined as previously described (19, 201. In earlier years, antigen expression was evaluated by microscopic analysis of indirect immunofluorescence, whereas, since 1991 cell surface antibody binding has been evaluated by flow cytometry using a FACScan and the Lysys II software [3]. The blast count in all patients’ samples ranged from 80 to 99%. Cytogenetic analysis was performed at different ECOG institutions. RESULTS We report on six patients with acute leukemia who had a t(lO;ll)(pll-15;ql3-23), either alone (patients 1, 3, and 4) or in combination with other abnormalities, including del(7q) (patient 2) and trisomy 19 (patients 5 and 6) (Table 1). In patients 5 and 6, an apparently normal, diploid karyotype was seen in 80% and 30% of metaphases, respectively. Serial chromosome analyses over the course of the disease in patients 2 and 3 showed persistence of initial aberrations at the time of first and second relapse in both patients. Breakpoints on lop varied, affecting lop11 in 3 cases and lOplZ,lOp13, and lop15 in one case each, confirming the reported heterogeneity in lop breakpoints involved in llq rearrangements (211. Patients 1 through 4 presented morphologically as AMoL (FAB-M5A) (Table 2). Immunophenotypically (Tables 2 and 3), patients 1 and 2 had a differentiated AML and patients 3 and 4 were monocytic. The stem cell marker terminal deoxynucleotidyl transferase (TdT), which is more commonly expressed in ALL [22], was detected in 30% and 99% of nonlymphoid blast cells in

Table 1

Cytogenetic

Patient

patients 1 and 2, respectively, and one of three patients tested for lymphoid-associated antigens expressed the T-cell markers CD2 and CD7 (patient 4), while B-cell-associated antigens were generally absent. Typically for AMOL [22], myeloperoxidase expression was low in the AMOL cases when determined by antibody staining (~-IO%) (Table 2). Patients 5 and 6 had leukemia with FAB-Ll characteristics. Immunophenotypically, patient 5 was an undifferentiated ALL (TdT+, HLA-DR+, POX-), with coexpression of CD7 and CD19 but absence of any other lymphoid antigens (intracytoplasmic CD22-, CDlO-, CD24-, CD2-) and expression of the myelomonocytic antigens CD33 and CD13 by almost half the blast cells. Patient 6, however, despite Ll features, typed as myelomonocytic leukemia with strong myeloperoxidase expression and positivity for the monocyte-specific antigen CD14 on 38% of blast cells. In addition, all blasts from this patient stained for the T-cell-associated antigen CD7 and, in part, for CD2. Serial laboratory studies were feasible in patients 2 and 3. In patient 2, repeated relapses were not associated with a change in morphology or cytogenetics and, in terms of the immunophenotype, resulted in increased myeloperoxidase expression without other antigens being newly expressed or lost (not shown). In patient 3, on the other hand, at the time of first relapse following a 4-month remission, blast cells with FAB-L2 morphology replaced the original FAB-M5A cells. Immunologically, these lymphoid-appearing cells were TdT+ and expressed the Tcell-associated antigens CD7, CD2, and CDl, while lacking other lymphoid- or myeloid-associated antigens. The marker profile, therefore, fit the diagnosis of pre-T ALL. At the time of second relapse, the L2 blast cells were still TdT and CD7 positive but also expressed CD33 and, in a small fraction of cells, CDw65, CD15, and CDllb, suggesting myelomonocytic features (Table 3). These immunophenotypic changes were not associated with a change in the karyotype, which remained positive for t(l9;ll) as the sole cytogenetic abnormality both at first and second relapse of this patient’s leukemia.

DISCUSSION We report on the biologic characteristics of six patients with t(lo;ll)(pll-p15;q13-q23), which accounted for