|
|||||||||
|
|
|
|
|
|
|
|
|
|
|
Blood, Vol. 94 No. 11 (December 1), 1999:
pp. 3707-3716
By
From the Departments of Pathology and Laboratory Medicine, St
Jude Children's Research Hospital, and University of Tennessee,
Memphis, TN; Children's Hospital of Michigan, Barbara Ann Karmanos
Cancer Institute, and Wayne State University, Detroit, MI; POG
Statistical Office and the Department of Statistics, The University of
Florida, Gainesville, FL; Baylor College of Medicine, Texas Children's
Hospital, Houston, TX; Harvard Medical School and Massachusetts General
Hospital, Boston, MA; and University of Alabama at Birmingham,
Birmingham, AL.
We determined the type and frequency of chromosomal aberrations in
leukemic cells of 478 children diagnosed with acute myeloid leukemia
and enrolled in the Pediatric Oncology Group study 8821. Of the 478 cases, 109 (22.8%) had normal karyotypes. Chromosomal abnormalities of
280 patients (58.6%) were classified into subgroups: 11q23
abnormalities (n = 88, 18.4%), t(8;21) (n = 56, 11.7%), t(15;17) (n = 55, 11.5%), inv(16)/t(16;16) (n = 28, 5.9%),
trisomy 8 alone (n = 10, 2.1%), monosomy 7 (n = 9, 1.9%),
non-Down-associated trisomy 21 alone (n = 7, 1.5%), and rare
recurrent chromosomal translocations (n = 27, 5.6%). The remaining
89 patients (18.6%) had miscellaneous clonal abnormalities. Overall,
84.9% of the children achieved a complete remission; the 4-year
event-free survival (EFS) estimate was 33.8% ± 2.4%.
Remission rates were significantly higher (96.4%,
P = .011) for patients with t(8;21) and inv(16)/t(16;16)
but significantly lower (74.5%, P = .022) for those with
t(15;17). The 4-year survival rate for all patients was 43.5% ± 2.4%; for those with an inv(16)/t(16;16), 75.0% ± 8.6%; a normal
karyotype, 53.8% ± 4.9%; a t(8;21), 51.6% ± 7.3%; a t(15;17),
39.8% ± 6.9%; and an 11q23 abnormality, 32.9% ± 5.1%. Four-year
EFS estimates for patients with inv(16)/t(16;16) (58.2% ± 10.9%,
P = .007), t(8;21) (45.1% ± 7.7%,
P = .014), or normal karyotypes (43.1% ± 5.0%,
P = .012) were higher than the 4-year EFS estimate for all
patients, but EFS estimates for patients with t(15;17)
(19.6% ± 8.0%, P = .033) or 11q23 abnormalities (23.8% ± 4.8%, P = .0013) were lower. EFS estimates
did not differ significantly among 11q23 subgroups. Limited analysis
suggested that patients with inv(16) can be salvaged better following
relapse than those with t(8;21). Thus, patients with an
inv(16)/t(16;16) may have high survival rates when treated with
chemotherapy alone.
IN ACUTE MYELOID LEUKEMIA (AML), various
chromosomal abnormalities have been recognized as primary pathogenetic
changes. Clonal chromosomal abnormalities are found in approximately
80% of children with AML.1-6 Data from International
Workshops and large prospective studies of adults and children have
shown correlations between specific recurrent chromosomal abnormalities
and clinico-biological characteristics and outcome.7-9
Favorable-prognosis karyotypes in patients with AML include
constitutional trisomy 21 (Down syndrome), and t(8;21)
associated with myelocytic leukemia (AML French-American-British [FAB]-M2) and inv(16)/t(16;16), which is primarily associated with
myelomonocytic leukemia and increased abnormal eosinophils (AML
FAB-M4eo). Poor-prognosis karyotypes include 11q23 abnormalities in
young patients and monosomy 7. Recently, the use of chemotherapy and
all-trans-retinoic acid (ATRA) has improved outcome for
patients with t(15;17)-associated acute promyelocytic leukemia
(APL).10,11
With current treatment protocols, only 30% to 50% of children with
AML will have a successful outcome.3,5,7,12 Therefore, it
is important to correlate characteristic cytogenetic subgroups with
disease outcome to identify patients that may benefit from prospective
individualized therapy.12-14 We report here the results of
the cytogenetic analysis of a cooperative group study, the largest
study of chromosomal abnormalities in children with AML published to
date. The 478 cases were segregated into cytogenetic subgroups for
comparison of presenting clinical and biological features, response to
induction therapy, and long-term outcome.
Patients
Cytogenetic Studies
Statistical Analysis Cases were segregated into commonly accepted cytogenetic subgroups for evaluation of clinical features at presentation, response to treatment, and outcome. Patients were each assigned to a single subgroup reflecting the primary change observed. The categories were normal karyotype, t(8;21), t(15;17), inv(16) or t(16;16), 11q23 abnormalities, monosomy 7, trisomy 8 or trisomy 21 alone, rare recurrent translocations [ie, t(10;11)(p13;q21), t(6;9)(p23;q34), t(3;5)(q25;q34), t(1;22)(p13;q13), and t(8;16)(p11;p13)], and miscellaneous (with single or multiple clonal abnormalities). A patient achieved remission if a marrow status of either M1 (<5% blast cells) or M2a (<15% blast cells) resulted after 2 courses of induction therapy. Event-free survival (EFS) was calculated from the date of registration until the earlier of the date of first relapse or the date of death. Overall survival was calculated from the date of resistance to DAT (daunomycin, cytarabine [ara-c], and 6-thioguanine), regardless of cause. The actuarial curves of EFS for various cytogenetic subgroups were generated according to the Kaplan-Meier method,20 and the log-rank test was used to compare survival rates.21 Median values were compared by the Wilcoxon rank sum test,22 and the homogeneity of proportions was tested by the chi-square test. The P values were computed from the 2-sided test by comparing the groups of patients with and without the characteristic of interest.
Of the 478 children diagnosed with de novo AML and an evaluable
chromosome analysis, 109 (22.8%, 57 males and 52 females) had an
apparently normal karyotype (Table 1). Of
the remaining 369 cases with an abnormal karyotype (77.2% of the study
population), 280 (75.9%) had consistent or recurrent abnormalities,
and 89 (18.6%) had miscellaneous chromosomal changes (Fig
1 and Table 2).
Modal Number Pseudodiploidy was found in 245 cases, representing 51.3% of all cases. All but 1 of the 47 hypodiploid cases had 45 chromosomes; the remaining case had 41 chromosomes. In most of the cases with 45 chromosomes, hypodiploidy was the result of the loss of a sex chromosome (n = 26) or monosomy 7 (n = 9). Most of the hyperdiploid cases had 47 (n = 53) or 48 chromosomes (n = 12); an additional 2 cases each had 49 and 50 chromosomes. In addition, there were 5 patients with 51 to 58 chromosomes in the leukemic lines, and 3 with 91 to 93 chromosomes and structural abnormalities. Therefore, hyperdiploidy 47-50 accounted for 14.4% of the study population, hyperdiploidy 51-58 for 1.1%, and hyperdiploidy 91-93 for 0.6%.Common Recurrent Chromosomal Abnormalities t(8;21)(q22;q22). This translocation, found in 56 patients (11.7%), was the most frequently observed translocation. Among the cases characterized by this aberration, 33 (58.9%) had 46 chromosomes, 21 (37.5%) had 45, and 2 (3.6%) had 47. This translocation was the sole structural abnormality in 22 (39.3%) cases, and 4 had a complex t(8;21). The 21 cases of t(8;21) with a modal number of 45 all had a loss of a sex chromosome. An additional 2 cases had a loss of a sex chromosome as well as other numerical abnormalities, and in another 2 cases, loss of the Y chromosome was found only in the sideline. Loss of the Y chromosome occurred more frequently (16 of 29 males) than loss of the X chromosome (9 of 27 females). An additional chromosome was identified in 4 cases (+4, n = 2; +8, n = 1; +15, n = 1). Secondary structural changes (n = 16) included deletion of 9q in 6 of the 56 cases (10.7%). Abnormalities of 7q were seen in 5 cases (8.9%); 2 cases each had a del(7q) or der(7q), and 1 had a dup(7)(q22q32). The remaining 5 cases had random secondary structural aberrations. t(15;17)(q22;q12-21).
The t(15;17) was observed in 55 of the 478 cases (11.5%); the modal
number was 45 (n = 3), 46 (n = 50), or 47 (n = 2). This rearrangement was the sole structural abnormality in 48 (87.3%) of the
cases in this subgroup. The only additional recurrent structural aberration observed with the t(15;17) was del(9q), which was seen in a
single case. The t(15;17) subgroup included 2 cases with i(der 17q), 1 of which had the isochromosome in the sideline (indicating clonal
evolution), and 3 cases with complex t(15;17) rearrangements. Additional numerical abnormalities included +8 (n = 2), inv(16)(p13q22) or t(16;16)(p13;q22). Twenty-eight cases (5.9% of the study population) were assigned to this subgroup: 26 with inv(16) and 2 with t(16;16). The inv(16)/t(16;16) was the sole abnormality in 22 of these 28 cases (78.6%). Associated numerical abnormalities were +8 (n = 1), +21 (n = 1), and +22 (n = 3); an additional case had a del(9q) as an associated aberration. Because of the strong association between +22 and inv(16), 2 additional cases, in which +22 was apparently the sole chromosomal abnormality, were reevaluated for inv(16). However, we were unable to document the presence of inv(16) in either of these cases. 11q23 abnormalities. The most frequent chromosomal breakpoint in the present series occurred in chromosome 11 at q23; this abnormality was identified in 88 patients (18.4% of the study population). These cases were further classified into the following subgroups: t(9;11)(p22;q23) (n = 35), t(11;19)(q23;p13.1) (n = 9), t(11;19)(q23;p13.3) (n = 10), and other chromosomal aberrations involving the 11q23 region (n = 28). t(9;11)(p22;q23). Breakpoints at 9p22 and 11q23 were identified in 35 cases (7.3% of the study population). In 24 of these 35 cases, the t(9;11) was the sole chromosomal aberration, and most (32 cases) had a modal chromosome number of 46. Complex rearrangements of 9p22 and 11q23 with 14q24, 20p13, or 22q13 were seen in one case each. Only 1 of the 35 patients had an insertion [ins(9;11)(p21;q13q23)]; this case also showed another breakpoint at 11q23 [t(11;12)(q23;p13)]. An additional 2 cases each were associated with i(1)(q10) or +8; 2 other cases had +6, which was seen in the sidelines. t(11;19)(q23;p13.1) and t(11;19)(q23;p13.3). The t(11;19) rearrangement was observed in 19 cases (4.0% of the study population), with breakpoints at 19p13.1 (n = 9) and at 19p13.3 (n = 10). The distribution of modal numbers was 46 (16 cases), 48 (1 case), 49 (1 case), and 50 (1 case). In 12 patients (63.2% of this subgroup), the t(11;19) was the only abnormality; in another 2 patients, the rearrangement was complex. None of the cases with a breakpoint at 19p13.1 had additional chromosomal aberrations. Three t(11;19)(q23;p13.3) cases had an extra copy of the der(19)t(11;19) as well as trisomy 8. del(11)(q23). Of the 6 cases with deletion at 11q23 (the region of the MLL gene), it was the sole chromosomal aberration in 3, and in none of these 6 cases could a translocation be identified by conventional G-banding techniques. Currently, it is recommended that newer molecular cytogenetic techniques be used, like chromosome 11 painting, and fluorescence in situ hybridization (FISH) or Southern assay with the MLL probe, to rule out a subtle translocation and to assess whether the MLL is rearranged. Rare Recurrent Chromosomal Abnormalities t(10;11)(p13;q21).
Assigning the specific breakpoint occasionally was problematic for the
9 cases (1.9% of the study population) with a t(10;11)(p13;q21); some
karyotypes were read as t(10;11)(p13 or p14;q14.2 or q21). The
t(10;11)(p13;q21) was the sole chromosomal aberration in 2 cases, and
+8 and t(6;9)(p23;q34). Seen in 6 patients (1.3% of the study population), the t(6;9) was the sole abnormality in 5 cases. The remaining case had a sideline with +4. t(3;5)(q25;q34). In all 5 cases, the t(3;5) was the sole chromosomal aberration. In addition, 1 patient had a sideline that contained extra chromosomes. t(1;22)(p13;q13). In 2 of the 4 cases in this subgroup, the t(1;22) was the only abnormality; the other 2 had hyperdiploid karyotypes (54 and 58 chromosomes), both with an extra der(1)t(1;22). Consistent with this cytogenetic finding, 3 of the cases had FAB-M7 morphology, and 1 patient presented with granulocytic sarcoma. t(8;16)(p11;p13). The t(8;16) was the sole abnormality in 1 of the 3 cases with this aberration. Abnormalities of chromosomes 7 and 5.
Monosomy 7 was the sole abnormality in 6 of the 9 cases in this
subgroup (1.9% of the study population); 2 additional patients also
had +12 or +21. The remaining patient had a very complex karyotype that
included monosomy 5. Other abnormalities resulting in partial loss of
7q were identified in 12 cases. Deletion accounted for 4 of these
cases. The del(7)(q31) or del(7)(q21), seen in 1 case each, were
secondary changes associated with t(8;21). An additional case had a
del(7)(q32q35) as a component of a complex karyotype. The remaining
case characterized by a deletion in 7q had del(7)(q11) in the main line
and r(7q) in the sideline. Ring formations of chromosome 7 were seen in
2 additional cases, 1 of which had r(7)(p15q35) as a secondary change.
In the other case, the ring was one of the many aberrations observed in
a patient with Fanconi anemia (Table 2, case no. 60). An isochromosome of 7p resulted in the loss of 7q in 2 patients. In 3 cases, DNA of
unknown origin was attached to the q arm of chromosome 7, resulting in
add(7q). The breakpoints differed in all 3 patients, of which 2 also
had t(8;21), and 1 also had t(15;17). The 7q loss in the remaining case
was due to der(19)t(7;19)(p13;p11). Therefore, these 12 cases were not
included in this series as examples of
Trisomy 8. An extra chromosome 8 was observed in 40 cases (8.4% of the study population); in 10 (2.1%) patients, it was the sole chromosomal abnormality. Therefore, trisomy 8 was the most frequent numerical chromosomal abnormality seen in the present series of patients with childhood AML. The +8 was seen with other recurrent (18 cases) and nonrecurrent (12 cases) changes, but these 30 cases were not incorporated in the +8 subgroup for further analysis because they were interpreted as secondary changes. Trisomy 21. Acquisition of an extra chromosome 21 occurred in 26 cases and was the sole chromosomal aberration in 7. The karyotype of 1 of these 7 cases was 93,XXXX,+21. Trisomy 21 was seen with other recurrent (7 cases) and nonrecurrent (12 cases) changes; like that for the +8 subgroup, the analysis was restricted to cases with a single extra 21 chromosome. Other types of trisomy and monosomy. Trisomy of chromosome X, 4, or 22 was the sole abnormality in 2 cases each, and 1 case each showed gains of chromosomes 6, 11, or 19. Cases in which the loss of a chromosome was the sole aberration were rare and included 1 case each of monosomy X or 19 (Table 2). Miscellaneous Clonal Abnormalities This group includes 89 patients with various clonal abnormalities not represented by other subgroups (Table 2). A single abnormal clone was seen in 36 cases; 2 or more abnormal clones occurred in the remaining 53. Most of these cases are discussed in the following section. Noteworthy are rare abnormalities that have been previously reported, which include t(3;21)(q26.3;q22) (Table 2, case no. 33), and t(16;21)(p11.2;q22) (case no. 53).24,25Deletion. A total of 67 deletions were observed, the majority of which were secondary changes. Deletion was the sole acquired abnormality in only 8 cases: 3 cases with del(11)(q23), del(5q) and del(9q) in 2 cases each, and 1 case each with a deletion of 3p or 16q. No corresponding molecular or FISH analysis was done to determine whether subtle translocations were present in any of these cases. Patients who had deletion of 5q (n = 4) or 7q (n = 4) were discussed previously. Duplication. In 4 of the 9 cases with duplication, the abnormality occurred in the q arm of chromosome 1. The remaining cases showed duplications of 6q, 7q, 8p, 10q, and 11q (1 each). All of these 9 cases had additional chromosomal abnormalities. Isochromosomes.
Of the 9 cases with an isochromosome, 2 had an i(1q), which was
associated with t(9;11) and FAB M5 morphology. An additional 2 cases
had i(7)(p10) as the sole abnormality; because the consequence of this
isochromosome is loss of the 7q arm, these cases were considered to be
7q Inversion. Inversions were observed in 41 cases: inv(16) (n = 26; discussed previously), inv(11) [n = 4; inv(11)(p13q11), inv(11)(p13q14), inv(11)(p13q23), or inv(11)(q21q23)], inv(8) (n = 3), inv(17) (n = 2). Other chromosomes were involved in the remaining 6 cases. Identical breakpoints were detected only in the inv(16). The inv(3)(p25q21) seen in our patients differs from the recurrent inv(3)(q21q26) that is typically seen in adults with AML.8 Among the 15 non-inv(16) cases, the inversion was the sole abnormality only in the patient with inv(19)(p13q12). Therefore, other than those involving chromosome 16, most of the inversions appear to be secondary changes. Insertion. Of the 8 cases with this type of abnormality, 4 were included in the 11q23 subgroup. The remaining 4 insertions affected various chromosomes and were part of complex karyotypes. Dicentric chromosomes. Only 2 cases had dicentric chromosomes. A dic(16;21)(q11;p11) was the sole chromosomal abnormality in 1 case. Ring chromosomes. A total of 5 cases had a ring chromosome: r(6), r(16)(p13q24), r(7)(p22q31), r(7)(p15q35), and r(?). Presenting Features and Outcome The 478 patients in our study population were assigned to 1 of 7 groups [ie, normal karyotype, t(8;21), t(15;17), inv(16), 11q23 abnormalities, rare recurrent abnormalities, and miscellaneous aberrations] according to the primary chromosomal characteristic. Except when noted, reported differences in clinico-biological features reflect the comparison between patients with or without 1 of these 7 cytogenetic characteristics (Table 1).
We compared our findings with those of 5 previously reported series
with cytogenetic data,1-5 representing a total of 926 cases
of childhood AML (Table 4). Cytogenetic
analysis showed clonal abnormalities in 75% of those earlier cases, in
which t(8;21) is the most commonly observed single structural
abnormality (13% of patients, similar to our finding of 12%). The
t(15;17) was observed in 8% of the previously reported patients.
However, patients with APL sometimes receive therapies that are
different than those used to treat other types of AML.10,11
Such patients may have been omitted from the earlier series, thereby
skewing the reported incidence of t(15;17). In this study, patients
with APL were not excluded from the analysis and accounted for 11% of
our population.
Institutions and Grant Numbers of Participants
The authors thank V. Turner for her secretarial assistance in preparing
this manuscript, and A. Frazier and J.C. Jones for editorial
assistance. The participating Pediatric Oncology Group (POG)
Institutions and their Grant support are listed in the
Appendix.
Submitted November 19, 1998; accepted August 3, 1999.
Supported in part by grants from the National Institutes of
Health (CA-21765, CA-03161, CA-05587, CA-07431, CA-11233, CA-15525, CA-15898, CA-15989, CA-20549, CA-25408, CA-28383, CA-28439, CA-28476, CA-29139, CA-29293, CA-29691, CA-30969, CA-32053, CA-33587, CA-33603, CA-33625, CA-41573, CA-69177, and CA-69428), and by American Lebanese Syrian Associated Charities (ALSAC). Additional grant support is listed
in the Appendix.
The publication costs of this
article were defrayed in part by
page charge payment. This article
must therefore be hereby marked
"advertisement"
in accordance with 18 U.S.C. section
1734 solely to indicate this fact.
Address reprint requests to Susana C. Raimondi, PhD, Department of
Pathology, St Jude Children's Research Hospital, 332 N
Lauderdale, Memphis, TN 38105; e-mail: susana.raimondi{at}stjude.org.
1.
Leverger G, Bernheim A, Daniel M-T, Flandrin G, Schaison G, Berger R:
Cytogenetic study of 130 childhood acute nonlymphocytic leukemias.
Med Pediatr Oncol
16:227, 1988[Medline]
[Order article via Infotrieve]
2.
Raimondi SC, Kalwinsky DK, Hayashi Y, Behm FG, Mirro J Jr, Williams DL:
Cytogenetics of childhood acute nonlymphocytic leukemia.
Cancer Genet Cytogenet
40:13, 1989[Medline]
[Order article via Infotrieve]
3.
Martinez-Climent JA, Lane NJ, Rubin CM, Morgan E, Johnstone HS, Mick R, Murphy SB, Vardiman JW, Larson RA, Le Beau MM, Rowley JD:
Clinical and prognostic significance of chromosomal abnormalities in childhood acute myeloid leukemia de novo.
Leukemia
9:95, 1995[Medline]
[Order article via Infotrieve]
4.
Leblanc T, Auvrignon A, Michel G, Ansoborlo S, van den Akker J, Nelken B, Capodano A-M, Landman-Parker J, Baruchel A, Berger R, Schaison G, Leverger G:
Prognosis value of cytogenetics in 250 children with acute myeloblastic leukemia treated in the LAME 89/91 protocol.
Blood
88:634a, 1996 (abstr, suppl 1)
5.
Grimwade D, Walker H, Oliver F, Wheatley K, Harrison C, Harrison G, Rees J, Hann I, Stevens R, Burnett A, Goldstone A:
The importance of diagnostic cytogenetics on outcome in AML: Analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children's Leukaemia Group.
Blood
92:2322, 1998
6.
Woods WG, Nesbit ME, Buckley J, Lampkin BC, McCreadie S, Kim TH, Piomelli S, Kersey JH, Feig S, Bernstein I, Hammond D, for the Children's Cancer Study Group:
Correlation of chromosome abnormalities with patient characteristics, histologic subtype, and induction success in children with acute nonlymphocytic leukemia.
J Clin Oncol
3:3, 1985[Abstract]
7.
Barnard DR, Kalousek DK, Wiersma SR, Lange BJ, Benjamin DR, Arthur DC, Buckley JD, Kobrinsky N, Neudorf S, Sanders J, Miller LP, Shina DC, Hammond GD, Woods WG:
Morphologic, immunologic, and cytogenetic classification of acute myeloid leukemia and myelodysplastic syndrome in childhood: a report from the Childrens Cancer Group.
Leukemia
10:5, 1996[Medline]
[Order article via Infotrieve]
8.
The Fourth International Workshop on Chromosomes in Leukemia:
A prospective study of acute nonlymphocytic leukemia. Chicago, IL, September 2-7, 1982.
Cancer Genet Cytogenet
11:249, 1984[Medline]
[Order article via Infotrieve]
9.
Morphologic, immunologic, and cytogenetic (MIC) working classification of the acute myeloid leukemias. Second MIC Cooperative Study Group. Report on the Workshop held in Leuven, Belgium, September 15-17, 1986.
Cancer Genet Cytogenet
30:1, 1988[Medline]
[Order article via Infotrieve]
10.
Fenaux P, Chomienne C, Degos L:
Acute promyelocytic leukemia: Biology and treatment.
Semin Oncol
24:92, 1997[Medline]
[Order article via Infotrieve]
11.
Tallman MS, Andersen JW, Schiffer CA, Appelbaum FR, Feusner JH, Ogden A, Shepherd L, Willman C, Bloomfield CD, Rowe JM, Wiernik PH:
All- trans-retinoic acid in acute promyelocytic leukemia.
N Engl J Med
337:1021, 1997
12.
Kalwinsky DK, Raimondi SC, Schell MJ, Mirro J Jr, Santana VM, Behm F, Dahl GV, Williams D:
Prognostic importance of cytogenetic subgroups in de novo pediatric acute nonlymphocytic leukemia.
J Clin Oncol
8:75, 1990
13.
Head DR:
Revised classification of acute myeloid leukemia.
Leukemia
10:1826, 1996[Medline]
[Order article via Infotrieve]
14.
Ritter J:
Acute myeloid leukaemias:
Eur J Cancer
34:862, 1998
15.
Ravindranath Y, Yeager AM, Chang MN, Steuber CP, Krischer J, Graham-Pole J, Carroll AJ, Inoue S, Camitta B, Weinstein H, for the Pediatric Oncology Group:
Autologous bone marrow transplantation versus intensive consolidation chemotherapy for acute myeloid leukemia in childhood.
N Engl J Med
334:1428, 1996
16.
Carroll AJ, Castleberry RP, Crist WM:
Lack of association between abnormalities of the chromosome 9 short arm and either "lymphomatous" features or T cell phenotype in childhood acute lymphocytic leukemia.
Blood
69:735, 1987
17.
Raimondi SC, Mathew S, Pui C-H:
Cytogenetics as a diagnostic aid for childhood hematologic disorders, in
Hanausek M,
Walaszek Z
(eds):
Methods in Molecular Medicine: Tumor Marker Protocols, vol 14. Totowa, NJ, Humana, 1998, p 209
18.
Mitelman F:
ISCN 1991.Guidelines for Cancer Cytogenetics (1991). Basel, Switzerland, Karger, 1991
19.
Mitelman F:
ISCN 1995. An International System for Human Cytogenetic Nomenclature (1995). Basel, Switzerland, Karger, 1995
20.
Kaplan EL, Meier P:
Nonparametric estimation for incomplete observations.
J Am Statist Assoc
53:457, 1958
21.
Peto R, Peto J:
Asymptotically efficient rank invariate test procedures.
J Royal Stat Society
135:185, 1972
22.
Armitage P:
Statistical Method in Medical Research. Boston, MA, Blackwell Scientific, 1971
23.
Slovak ML, Kopecky KJ, Cassileth PA, Harrington DH, Theil K, Mohamed A, Chung A, Paietta E, Willman C, Head DR, Forman SJ, Appelbaum FR:
Karyotypic analysis predicts outcome of pre- and post-remission therapy in adult acute myeloid leukemia (AML): A SWOG/ECOG intergroup study.
Blood
92:678a, 1998 (abstr, suppl 1)
24.
Rubin CM, Larson RA, Anastasi J, Winter JN, Thangavelu M, Vardiman JW, Rowley J, Le Beau MM:
t(3;21)(q26;q22): A recurring chromosomal abnormality in therapy-related myelodysplastic syndrome and acute myeloid leukemia.
Blood
76:2594, 1990
25.
Kong X-T, Ida K, Ichikawa H, Shimizu K, Ohki M, Maseki N, Kaneko Y, Sako M, Kobayashi Y, Tojou A, Miura I, Kakuda H, Funabiki T, Horibe K, Hamaguchi H, Akiyama Y, Bessho F, Yanagisawa M, Hayashi Y:
Consistent detection of TLS/FUS-ERG chimeric transcripts in acute myeloid leukemia with t(16;21)(p11;q22) and identification of a novel transcript.
Blood
90:1192, 1997
26.
Shurtleff SA, Meyers S, Hiebert SW, Raimondi SC, Head DR, Willman CL, Wolman S, Slovak ML, Carroll AJ, Behm F, Hulshof MG, Motroni TA, Okuda T, Liu P, Collins FS, Downing JR:
Heterogeneity in CBF
27.
Ritter M, Thiede C, Schakel U, Schmidt M, Alpen B, Pascheberg U, Mohr B, Ehninger G, Neubauer A, for the AML-SHG Study Group:
Underestimation of inversion (16) in acute myeloid leukaemia using standard cytogenetics as compare |
POG 8821
TOP
ABSTRACT
INTRODUCTION
Y
(n = 1), and 
/MYH11 fusion messages encoded by the inv(16)(p13q22) and the t(16;16)(p13;q22) in acute myelogenous leukemia.
Blood
85:3695, 1995