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Translocation (1;14)(p34;q11) and trisomy 8 in a T -cell acute lymphoblastic Leukemia patient
I!LSEVI|!R
SHORT COMMUNICATIONS Translocation (1;14)(p34;q11) and Trisomy 8 in a T-Cell Acute Lymphoblastic Leukemia Patient Gregorio Angel Martin-Henao and Anna Sureda ABSTRACT: A case ofT-cell acute lymphoblastic leukemia (T-ALL) in a 25-year-old man cytogenetically characterized by a t(1;14)(p34;q11) and trisomy 8 is reported. These chromosome abnormalities were observed in 82% of the analyzed metaphases. Fluorescence in situ hybridization (FISH) with a probe for the centromere of chromosome 8 was used to correlate cellular morphology in bone marrow (BM) cells with May-Griinwald-Giemsa smears and the cytogenetic alterations. By FISH analysis, trisomy 8 (and presumably the associated t[1;14]) was demonstrated only in l y m p h o i d blast cells but not in the rest of the cells belonging to other hemotopoietic lineages.
INTRODUCTION Clonal chromosomal abnormalities have been found in more than 90% of ALL cases [1]. Nevertheless, in patients with T-ALL the frequency of normal karyotypes at presentation can be as high as 26% [2]. Moreover, in T-ALLpseudodiploid karyotypes are much more frequent than hypodiploid and hyperdiploid ones [3]. The frequency of the t(1;14)(p34;q11) is 3% in children with T-ALL and seems to be limited to this disorder [4]. Trisomy 8 is a frequent finding in myeioid malignancies, rarely reported in ALL as the sole abnormality [5, 6]. We present the first case of t(1;14) and trisomy 8, as well as other changes, in a patient with T-ALL. To correlate morphologic features with chromosome findings we performed immunophenotype, cytogenetic, and FISH analysis on BM cells.
MATERIALS AND METHODS Case Report A 25-year-old male was admitted because of a 1-week history of increasing dyspnea, dry cough, and left upper quadrant pain. Physical examination was unremarkable except for hypophonesis in the lower left hemithorax and splenomegaly. Chest X-rays disclosed a widened mediastinum. The white blood cell count was 305 × 10O/L with 85% blast cells, hematocrit 43%, and platelet count 84 xl0Y/L. Uric acid was 508 I~mol/L (normal value, 227-459 I~mol/L) and
From the Departamento de Hematologia, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. Address repr/nt requests to: Gregor/oAngel Mart in Henao, Departamento de Hematologfa, Hospital de la Santa Creu i Sant Pau, Antoni Maria i Claret, 167, 08025 Barcelona, Spain. Received November 10, 1993; accepted March 30, 1994. Cancer Genet Cytogenet 79:177-181 (1995) © Elsevier Science Inc.. 1995 655 Avenue of the Americas. New York. NY 10010
LDH was 10,800 U/L (230-460 U/L}. BM aspirate was hypercellular with an 85% infiltration of lymphoid blasts (L2 following the French-American-British [FAB]classification) and frequent mitoses. Surface membrane markers of the blastic cell population were studied using direct and indirect immunofluorescence and were examined with the aid of a FACScan flow cytometer (Becton Dickinson, Mountain View, CA). The following monoclonal antibodies were analyzed: CD1, CD2, CD3, CD4, CD5, CD7, CD8, CD19, CD20, CD33, CD34, CD36, CD41, and anti-HLA-DR. The immunophenotype profile of the blast cell population was consistent with a T-ALL, being positive for CD2, CD3 (cytoplasmic), CD4, CD5, CD7, and CD8, and negative for the rest. Cytogenetic analysis was performed in direct BM preparations after a 24-hour culture without mitogens, and chromosomes were stained by a G banding technique. Karyotype according to the International System for Human Cytogenetic Nomenclature (ISCN) [7] was as follows: 46,XY/47,XY,t(1;14)(p34;q11), + 8, - 9,9p +, + mar (Fig.l) in 16 of the 19 metaphases analyzed. Combined chemotherapy was administered and the patient entered complete remission on day +14.
Interphase Cytogenetic Study Morphologic analysis was performed on May-GrfinwaldGiemsa stained BM smears protected with coverslips. Photomicrographs of approximately 150 cells including mature myeloid, erythroid, and megakaryocitic elements were taken and a graduated microscope stage was used to note the location of each cell photographed. Coverslips were removed and the slides washed with xylol for 10 minutes. The slides were hybridized directly, without any pre-treatment, as previously described [8]. A biotin-labeled DNA probe directed to the centromere of chromosome 8 (Oncor, Inc., Gaithersburg, MD) was used and detected with fluorescein-labeled avidin (Oncor). The same microscope was used to locate the cells previously photographed.
0165-4608/95/$9.50 SSDI 0165-4608(94)00054-F
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Table 1
G - b a n d e d karyotype of the c l o n e s h o w i n g 47,XY, t ( 1 ; 1 4 ) ( p 3 4 ; q l l ) , + 8 , - 9 , 9 p + , + m a r .
Summary of reported patients with t(1;14)
Patient
Age/sex
Karyotype
Reference
1 2 :3 4 5 6 7 8 9
15/M 8/F 8/M 13/M 3/M 13/M 7/M 8/M 15/M
I91 11Ol [lOl 141 I41 141 141 141 1111
10 11
12/M 12/F
12
11/M
13 b 14
4/M 16/M
15
25/M
46,XY,t(1 ;14)(p32;qll),del(6)(q15q23) 46,XX,t(l;14)(p32;qll),del(6}(q2 lq25) 46,XY,t(l;14)(p32;q11) 46.XY,t(I ;14) (p34;q11) 46.XY,del(6)(ql 3q23),t(1;14)(p34;qll) 46,XY,del(6)(q13q23),t(1;14)(p34;qll) 46,XY,del(6)(q13q23),t(1;14)(p34;qll) 46,XY,t(1 ;14)(p34;ql 1) 46,XY,t(1 ;14)(p32;qll)/46,XY,t(1;14) (p32;qll),del(6)(qllq23) 46,XY,inv(9)(p 12ql 3)",t(1;14)(p34;ql 1) 46,X, - X,del(6)(q21q25),de|(9) (p13p22),t{l;14)(p34;qll), + mar 46,XY, - 4 , + 5, - 11,del(3)(p21), t(1;14)(p34;qll), + der(11)t(11;?)(q23;?) 46,XY,r(21 ),t(1 ;14)(p34;ql 1) 46,XY, - 14,del(1}(p33).del(1)(q11), del(l 3)(ql 4), + der(1)t(1;14)(p33;ql 1) 47,XY,t(1;14){p34;qll), + 8, - 9,9p +, + mar
CzConstitutional inv[9). b T-cell lymphoblastic lymphoma.
112] 113] 1131 1131 1141 Present case
179
F i g u r e 2 a) A May-Griinwald-Giemsa stained bone marrow smear ( × 100) showing blast cells, a small megakaryocyte and a cell from the gmnulocytic line. b) Fluorescence in situ hybridization with a chromosome 8 probe ( x 100) in the same cells. Blast cells show three hybridization signals and the rest only two.
180
G . A . Martin-Henao and A. Sureda
RESULTS AND DISCUSSION
REFERENCES
This is the first reported case ofa t(1;14)(p34;qll) and trisomy 8 in a T-ALL patient. Fourteen other cases of t(1;14)(p34;qla) with slight differences in the interpretation of the breakpoints have been described [4, 9-14] (Table 1). All of them were children or young adults and except for one case considered to be lymphoblastic l y m p h o m a [13], the rest were T-ALL, most of them with L1 morphology. It has been suggested that this translocation is limited to a subgroup of children with T-ALL [4]. At the molecular level, the transposition of TALl from its normal location on chromosome 1 into the T-cell receptor ct/6 c h a i n complex on chromosome 14 as a consequence of t(1;14)(p34;qll) has been related to the malignant transformation of thymocytes [15]. Our case was an adult patient with a high white blood cell count, a large mediastinal mass, and splenomegaly, as were those previously reported. In this case, lymphoblast morphology was L~. Cytogenetic analysis revealed a t(1;14)(p34;qll) and trisomy 8 in the same clone, an association never described in T-ALL. Kurzberg et al. [16] describe eight cases of T-ALL and CD7+, C D 4 - , CD8- phenotype, one of them previously reported [14], presenting with t(1;14)(p33;q11). They suggest that leukemias with this i m m u n o p h e n o t y p e represent a subgroup of leukemias arising from immature hematopoietic cells capable of differentiating to all lineages. In our case, t(1;14)(p34;q11) is related to a mature thymocyte phenotype [17]. Five cases of T-ALL with t(1;14) and mature phenotype (CDT+, CD3 +, CD4 +, CD8 + ) have been reported by Carrol et al. [4]. Four of them expressed one or more myeloidassociated antigens, suggesting a mixed lineage. Interestingly, our case did not coexpress myeloid antigens but presented with a cytogenetic abnormality classically found in myeloid malignancies. FISH studies suggested that leukemic lymphoblasts were the only cell lines involved in the clonal aberration, with no participation of the rest of the n o n - l y m p h o i d hematopoietic cell lines. By means of a centromeric probe directed to chromosome 8, we demonstrated three clear hybridization signals in blast cells by morphologic analysis but only two in myeloid, erythroid, and megakaryocytic precursors (Fig. 2). However, although we found cytogenetic clonality restriction in the blastic cell line, it cannot be concluded that the origin of the neoplastic clone is a lymphoid-restricted progenitor rather than a more undifferentiated one. Cytogenetic analysis of our patient also disclosed a monosomy 9 and 9p ÷, abnormalities reported to be frequent in ALL. It has been suggested that they identify a subgroup of patients with bulky disease at diagnosis and T phenotype [18], also present in our case. In conclusion, we report for the first time a t(1;14)(p34;q11) and trisomy 8, as well as other changes, in T-ALL. In this case, t(1;14)(p34;q11) could represent the primary chromosomal abnormality arising from a pluripotent hematopoietic progenitor [14] or from a precursor more committed to T lymphoid lineage. In this setting, trisomy 8 and abnormalities in chromosome 9 could be cytogenetic abnormalities acquired as a part of the multistep process of leukemogenesis.
1. Williams DL, Raimondi S, Rivem G, George S, Berard CW, Murphy B (1985): Presence of clonal chromosome abnormalities in virtually all cases of acute lymphoblastic leukemia. N Engl J Med 313:640-641. 2. Pui CH, Behm FG, Singh B, Schell MJ, Williams DL, Rivera GK, Kalwinsky DK, Sandlund Jr, Crist WM, Raimondi SC (1990): Heterogeneity of presenting features and their relation to treatment outcome in 120 children with T-cell acute lymphoblastic leukemia. Blood 75:174-179. 3. Raimondi SC, Behm, FG, Roberson PK, Pui CH, RiveraGK, Murphy SB, Williams DL (1988): Cytogenetics of childhood T-cell leukemia. Blood 72:1560-1566. 4. Carroll AJ, Crist WM, Link MP, Amylon MD, Pullen DJ, Ragab AH, Buchanan GR, Wimmer RS, Vietti TJ (1990): The t(1;14)(p34;q11) is non.random and restricted to T-cell acute lymphoblastic leukemia: A pediatric oncology group study. Blood 76:1220-1224. 5. Sandbert AA (1990): Chromosome changes and their significance in acute nonlymphocytic leukemia. In: The Chromosomes in Human Cancer and Leukemia, 2nd Ed. Elsevier Science Publishing Co., New York, pp. 223-312. 6. Garipidou V, Yamada T, Prentice HG, Secker-WalkerLM (1990): Trisomy 8 in acute lymphoblastic leukemia (ALL): A case report and update of the literature. Leukemia 4:717-719. 7. ISCN (1985): An International System for Human Cytogenetic Nomenclature, Harnden DG, Klinger HP (eds.) published in collaboration with Cytogenet Cell Genet (Karger, Basel, 1985); also in Birth Defects: Original Article Series, Vol. 21, No. 1 (March of Dimes Birth Defects Foundation, New York, 1985). 8. Anastasi J, Vardiman JW, Rudinsky R, Patel M, Nachman J, Rubin CH, Le Beau MM (1991}:Direct correlation of cytogenetic findings with cell morphology using hybridization: an analysis of suspicious cell in bone marrow specimens of two patients completing therapy for acute lymphoblastic leukemia. Blood 77: 2456-2462. 9. Mathieu-Mahul D, Bernheim A, Sigaux I~; Daniel MT, Larsen CJ, Berger R (1986): Translocation t(1;14)et remaniment du g~ne de la chaine alpha du ig,cepteur T dans une leuc~mie aigu/~lymphoblastique T. C RAcad Sc (Paris) 302:525-528. 10. Lampert F, Harbott J, Ritterbach J, Ludwig WD, Fonatseh C, Schwamborn D, Stier B, Gnekow A, Gerein V, Stollmann B, Jobke A, Janka-Schaub G (1988): T-cell acute childhood lymphoblastic leukemia with chromosome 14qll anomaly: a morphologic, immunologic, and cytogenetic analysis of 10 patients. Blut 56:117-123.
G.A. Martin-Henao is a recipient of grant 93/5176 from el Fondo de Investigaciones Sanitarias (FIS).
11. Berger R, Le Coniat M, Vecchione D, Derr~ J, Chen SJ (1990): Cytogenetic studies of 44 T-cell acute lymphoblastic leukemia. Cancer Genet Cytogenet 44:69-75. 12. SeckeroWalker LM, Chessell JM, Stewart EL, Swansbury GJ, Richards S, Lawler SD (1989): Chromosomes and other prognostic factors in acute lymphoblastic leukaemia: a long-term follow-up. Br J Haematol 72:336-342. 13. KanekoY, Frizzera G, Shikano T, KobayashiH, Maseki N, Sakurai M (1989): Chromosomal and immunophenotypic patterns in T cell acute lymphoblastic leukemia (T ALL) and lymphoblastic lymphoma (LBL). Leukemia 3:886-892. 14. Herschfield MS, Kurtzberg J, Harden E, Moore JO, Whang-Peng J, Haynes B (1984): Conversion of a stem cell leukemia from a T-lymphoid to a myeloid phenotype induced by the adenosine deaminase inhibitor 2'-deoxycoformycin. Proc Natl Acad Sci USA 81:253-257. 15. Chen Q, Cheng J-T, Tsai I,-H, Scheider N, Buchanan G, Carroll A, Crist W, Ozanne B, Siciliano MJ, Baer R (1990): The tal gene undergoes chromosome translocation in T cell leukemia and potentially encodes a helix-loop-helix protein. EMBO J 9: 415-424.
t(1;14) and ÷ 8 in T-Cell L y m p h o b l a s t i c L e u k e m i a
16. Kurtzberg J, Waldmann TA, Davey MP, Bigner SH, Moore JO, Hershfield MS, Haynes BJ (1989): CD7 ÷, CD4 - , CD8 - acute leukemia: A syndrome of malignant pluripotent lymphohematopoietic cells. Blood 73:381-390. 17. Pui CH, Behm FG, Crist WM (1993): Clinical and biologic rele-
181
vance of immunologic marker studies in childhood acute lymphoblastic leukemia. Blood 82:343-362. 18. Kowalczyk J, Sandberg AA (1983): A possible subgroup of ALL with 9p - . Cancer Genet Cytogenet 9:383-385.
SHORT COMMUNICATIONS Translocation (1;14)(p34;q11) and Trisomy 8 in a T-Cell Acute Lymphoblastic Leukemia Patient Gregorio Angel Martin-Henao and Anna Sureda ABSTRACT: A case ofT-cell acute lymphoblastic leukemia (T-ALL) in a 25-year-old man cytogenetically characterized by a t(1;14)(p34;q11) and trisomy 8 is reported. These chromosome abnormalities were observed in 82% of the analyzed metaphases. Fluorescence in situ hybridization (FISH) with a probe for the centromere of chromosome 8 was used to correlate cellular morphology in bone marrow (BM) cells with May-Griinwald-Giemsa smears and the cytogenetic alterations. By FISH analysis, trisomy 8 (and presumably the associated t[1;14]) was demonstrated only in l y m p h o i d blast cells but not in the rest of the cells belonging to other hemotopoietic lineages.
INTRODUCTION Clonal chromosomal abnormalities have been found in more than 90% of ALL cases [1]. Nevertheless, in patients with T-ALL the frequency of normal karyotypes at presentation can be as high as 26% [2]. Moreover, in T-ALLpseudodiploid karyotypes are much more frequent than hypodiploid and hyperdiploid ones [3]. The frequency of the t(1;14)(p34;q11) is 3% in children with T-ALL and seems to be limited to this disorder [4]. Trisomy 8 is a frequent finding in myeioid malignancies, rarely reported in ALL as the sole abnormality [5, 6]. We present the first case of t(1;14) and trisomy 8, as well as other changes, in a patient with T-ALL. To correlate morphologic features with chromosome findings we performed immunophenotype, cytogenetic, and FISH analysis on BM cells.
MATERIALS AND METHODS Case Report A 25-year-old male was admitted because of a 1-week history of increasing dyspnea, dry cough, and left upper quadrant pain. Physical examination was unremarkable except for hypophonesis in the lower left hemithorax and splenomegaly. Chest X-rays disclosed a widened mediastinum. The white blood cell count was 305 × 10O/L with 85% blast cells, hematocrit 43%, and platelet count 84 xl0Y/L. Uric acid was 508 I~mol/L (normal value, 227-459 I~mol/L) and
From the Departamento de Hematologia, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. Address repr/nt requests to: Gregor/oAngel Mart in Henao, Departamento de Hematologfa, Hospital de la Santa Creu i Sant Pau, Antoni Maria i Claret, 167, 08025 Barcelona, Spain. Received November 10, 1993; accepted March 30, 1994. Cancer Genet Cytogenet 79:177-181 (1995) © Elsevier Science Inc.. 1995 655 Avenue of the Americas. New York. NY 10010
LDH was 10,800 U/L (230-460 U/L}. BM aspirate was hypercellular with an 85% infiltration of lymphoid blasts (L2 following the French-American-British [FAB]classification) and frequent mitoses. Surface membrane markers of the blastic cell population were studied using direct and indirect immunofluorescence and were examined with the aid of a FACScan flow cytometer (Becton Dickinson, Mountain View, CA). The following monoclonal antibodies were analyzed: CD1, CD2, CD3, CD4, CD5, CD7, CD8, CD19, CD20, CD33, CD34, CD36, CD41, and anti-HLA-DR. The immunophenotype profile of the blast cell population was consistent with a T-ALL, being positive for CD2, CD3 (cytoplasmic), CD4, CD5, CD7, and CD8, and negative for the rest. Cytogenetic analysis was performed in direct BM preparations after a 24-hour culture without mitogens, and chromosomes were stained by a G banding technique. Karyotype according to the International System for Human Cytogenetic Nomenclature (ISCN) [7] was as follows: 46,XY/47,XY,t(1;14)(p34;q11), + 8, - 9,9p +, + mar (Fig.l) in 16 of the 19 metaphases analyzed. Combined chemotherapy was administered and the patient entered complete remission on day +14.
Interphase Cytogenetic Study Morphologic analysis was performed on May-GrfinwaldGiemsa stained BM smears protected with coverslips. Photomicrographs of approximately 150 cells including mature myeloid, erythroid, and megakaryocitic elements were taken and a graduated microscope stage was used to note the location of each cell photographed. Coverslips were removed and the slides washed with xylol for 10 minutes. The slides were hybridized directly, without any pre-treatment, as previously described [8]. A biotin-labeled DNA probe directed to the centromere of chromosome 8 (Oncor, Inc., Gaithersburg, MD) was used and detected with fluorescein-labeled avidin (Oncor). The same microscope was used to locate the cells previously photographed.
0165-4608/95/$9.50 SSDI 0165-4608(94)00054-F
178
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Figure
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Table 1
G - b a n d e d karyotype of the c l o n e s h o w i n g 47,XY, t ( 1 ; 1 4 ) ( p 3 4 ; q l l ) , + 8 , - 9 , 9 p + , + m a r .
Summary of reported patients with t(1;14)
Patient
Age/sex
Karyotype
Reference
1 2 :3 4 5 6 7 8 9
15/M 8/F 8/M 13/M 3/M 13/M 7/M 8/M 15/M
I91 11Ol [lOl 141 I41 141 141 141 1111
10 11
12/M 12/F
12
11/M
13 b 14
4/M 16/M
15
25/M
46,XY,t(1 ;14)(p32;qll),del(6)(q15q23) 46,XX,t(l;14)(p32;qll),del(6}(q2 lq25) 46,XY,t(l;14)(p32;q11) 46.XY,t(I ;14) (p34;q11) 46.XY,del(6)(ql 3q23),t(1;14)(p34;qll) 46,XY,del(6)(q13q23),t(1;14)(p34;qll) 46,XY,del(6)(q13q23),t(1;14)(p34;qll) 46,XY,t(1 ;14)(p34;ql 1) 46,XY,t(1 ;14)(p32;qll)/46,XY,t(1;14) (p32;qll),del(6)(qllq23) 46,XY,inv(9)(p 12ql 3)",t(1;14)(p34;ql 1) 46,X, - X,del(6)(q21q25),de|(9) (p13p22),t{l;14)(p34;qll), + mar 46,XY, - 4 , + 5, - 11,del(3)(p21), t(1;14)(p34;qll), + der(11)t(11;?)(q23;?) 46,XY,r(21 ),t(1 ;14)(p34;ql 1) 46,XY, - 14,del(1}(p33).del(1)(q11), del(l 3)(ql 4), + der(1)t(1;14)(p33;ql 1) 47,XY,t(1;14){p34;qll), + 8, - 9,9p +, + mar
CzConstitutional inv[9). b T-cell lymphoblastic lymphoma.
112] 113] 1131 1131 1141 Present case
179
F i g u r e 2 a) A May-Griinwald-Giemsa stained bone marrow smear ( × 100) showing blast cells, a small megakaryocyte and a cell from the gmnulocytic line. b) Fluorescence in situ hybridization with a chromosome 8 probe ( x 100) in the same cells. Blast cells show three hybridization signals and the rest only two.
180
G . A . Martin-Henao and A. Sureda
RESULTS AND DISCUSSION
REFERENCES
This is the first reported case ofa t(1;14)(p34;qll) and trisomy 8 in a T-ALL patient. Fourteen other cases of t(1;14)(p34;qla) with slight differences in the interpretation of the breakpoints have been described [4, 9-14] (Table 1). All of them were children or young adults and except for one case considered to be lymphoblastic l y m p h o m a [13], the rest were T-ALL, most of them with L1 morphology. It has been suggested that this translocation is limited to a subgroup of children with T-ALL [4]. At the molecular level, the transposition of TALl from its normal location on chromosome 1 into the T-cell receptor ct/6 c h a i n complex on chromosome 14 as a consequence of t(1;14)(p34;qll) has been related to the malignant transformation of thymocytes [15]. Our case was an adult patient with a high white blood cell count, a large mediastinal mass, and splenomegaly, as were those previously reported. In this case, lymphoblast morphology was L~. Cytogenetic analysis revealed a t(1;14)(p34;qll) and trisomy 8 in the same clone, an association never described in T-ALL. Kurzberg et al. [16] describe eight cases of T-ALL and CD7+, C D 4 - , CD8- phenotype, one of them previously reported [14], presenting with t(1;14)(p33;q11). They suggest that leukemias with this i m m u n o p h e n o t y p e represent a subgroup of leukemias arising from immature hematopoietic cells capable of differentiating to all lineages. In our case, t(1;14)(p34;q11) is related to a mature thymocyte phenotype [17]. Five cases of T-ALL with t(1;14) and mature phenotype (CDT+, CD3 +, CD4 +, CD8 + ) have been reported by Carrol et al. [4]. Four of them expressed one or more myeloidassociated antigens, suggesting a mixed lineage. Interestingly, our case did not coexpress myeloid antigens but presented with a cytogenetic abnormality classically found in myeloid malignancies. FISH studies suggested that leukemic lymphoblasts were the only cell lines involved in the clonal aberration, with no participation of the rest of the n o n - l y m p h o i d hematopoietic cell lines. By means of a centromeric probe directed to chromosome 8, we demonstrated three clear hybridization signals in blast cells by morphologic analysis but only two in myeloid, erythroid, and megakaryocytic precursors (Fig. 2). However, although we found cytogenetic clonality restriction in the blastic cell line, it cannot be concluded that the origin of the neoplastic clone is a lymphoid-restricted progenitor rather than a more undifferentiated one. Cytogenetic analysis of our patient also disclosed a monosomy 9 and 9p ÷, abnormalities reported to be frequent in ALL. It has been suggested that they identify a subgroup of patients with bulky disease at diagnosis and T phenotype [18], also present in our case. In conclusion, we report for the first time a t(1;14)(p34;q11) and trisomy 8, as well as other changes, in T-ALL. In this case, t(1;14)(p34;q11) could represent the primary chromosomal abnormality arising from a pluripotent hematopoietic progenitor [14] or from a precursor more committed to T lymphoid lineage. In this setting, trisomy 8 and abnormalities in chromosome 9 could be cytogenetic abnormalities acquired as a part of the multistep process of leukemogenesis.
1. Williams DL, Raimondi S, Rivem G, George S, Berard CW, Murphy B (1985): Presence of clonal chromosome abnormalities in virtually all cases of acute lymphoblastic leukemia. N Engl J Med 313:640-641. 2. Pui CH, Behm FG, Singh B, Schell MJ, Williams DL, Rivera GK, Kalwinsky DK, Sandlund Jr, Crist WM, Raimondi SC (1990): Heterogeneity of presenting features and their relation to treatment outcome in 120 children with T-cell acute lymphoblastic leukemia. Blood 75:174-179. 3. Raimondi SC, Behm, FG, Roberson PK, Pui CH, RiveraGK, Murphy SB, Williams DL (1988): Cytogenetics of childhood T-cell leukemia. Blood 72:1560-1566. 4. Carroll AJ, Crist WM, Link MP, Amylon MD, Pullen DJ, Ragab AH, Buchanan GR, Wimmer RS, Vietti TJ (1990): The t(1;14)(p34;q11) is non.random and restricted to T-cell acute lymphoblastic leukemia: A pediatric oncology group study. Blood 76:1220-1224. 5. Sandbert AA (1990): Chromosome changes and their significance in acute nonlymphocytic leukemia. In: The Chromosomes in Human Cancer and Leukemia, 2nd Ed. Elsevier Science Publishing Co., New York, pp. 223-312. 6. Garipidou V, Yamada T, Prentice HG, Secker-WalkerLM (1990): Trisomy 8 in acute lymphoblastic leukemia (ALL): A case report and update of the literature. Leukemia 4:717-719. 7. ISCN (1985): An International System for Human Cytogenetic Nomenclature, Harnden DG, Klinger HP (eds.) published in collaboration with Cytogenet Cell Genet (Karger, Basel, 1985); also in Birth Defects: Original Article Series, Vol. 21, No. 1 (March of Dimes Birth Defects Foundation, New York, 1985). 8. Anastasi J, Vardiman JW, Rudinsky R, Patel M, Nachman J, Rubin CH, Le Beau MM (1991}:Direct correlation of cytogenetic findings with cell morphology using hybridization: an analysis of suspicious cell in bone marrow specimens of two patients completing therapy for acute lymphoblastic leukemia. Blood 77: 2456-2462. 9. Mathieu-Mahul D, Bernheim A, Sigaux I~; Daniel MT, Larsen CJ, Berger R (1986): Translocation t(1;14)et remaniment du g~ne de la chaine alpha du ig,cepteur T dans une leuc~mie aigu/~lymphoblastique T. C RAcad Sc (Paris) 302:525-528. 10. Lampert F, Harbott J, Ritterbach J, Ludwig WD, Fonatseh C, Schwamborn D, Stier B, Gnekow A, Gerein V, Stollmann B, Jobke A, Janka-Schaub G (1988): T-cell acute childhood lymphoblastic leukemia with chromosome 14qll anomaly: a morphologic, immunologic, and cytogenetic analysis of 10 patients. Blut 56:117-123.
G.A. Martin-Henao is a recipient of grant 93/5176 from el Fondo de Investigaciones Sanitarias (FIS).
11. Berger R, Le Coniat M, Vecchione D, Derr~ J, Chen SJ (1990): Cytogenetic studies of 44 T-cell acute lymphoblastic leukemia. Cancer Genet Cytogenet 44:69-75. 12. SeckeroWalker LM, Chessell JM, Stewart EL, Swansbury GJ, Richards S, Lawler SD (1989): Chromosomes and other prognostic factors in acute lymphoblastic leukaemia: a long-term follow-up. Br J Haematol 72:336-342. 13. KanekoY, Frizzera G, Shikano T, KobayashiH, Maseki N, Sakurai M (1989): Chromosomal and immunophenotypic patterns in T cell acute lymphoblastic leukemia (T ALL) and lymphoblastic lymphoma (LBL). Leukemia 3:886-892. 14. Herschfield MS, Kurtzberg J, Harden E, Moore JO, Whang-Peng J, Haynes B (1984): Conversion of a stem cell leukemia from a T-lymphoid to a myeloid phenotype induced by the adenosine deaminase inhibitor 2'-deoxycoformycin. Proc Natl Acad Sci USA 81:253-257. 15. Chen Q, Cheng J-T, Tsai I,-H, Scheider N, Buchanan G, Carroll A, Crist W, Ozanne B, Siciliano MJ, Baer R (1990): The tal gene undergoes chromosome translocation in T cell leukemia and potentially encodes a helix-loop-helix protein. EMBO J 9: 415-424.
t(1;14) and ÷ 8 in T-Cell L y m p h o b l a s t i c L e u k e m i a
16. Kurtzberg J, Waldmann TA, Davey MP, Bigner SH, Moore JO, Hershfield MS, Haynes BJ (1989): CD7 ÷, CD4 - , CD8 - acute leukemia: A syndrome of malignant pluripotent lymphohematopoietic cells. Blood 73:381-390. 17. Pui CH, Behm FG, Crist WM (1993): Clinical and biologic rele-
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vance of immunologic marker studies in childhood acute lymphoblastic leukemia. Blood 82:343-362. 18. Kowalczyk J, Sandberg AA (1983): A possible subgroup of ALL with 9p - . Cancer Genet Cytogenet 9:383-385.