t(5;12)(q13;p13) in acute myeloid leukemia with preceding granulocytic sarcoma

A 56-year-old woman was brought to the emergency room with gum swelling and pain. Biopsy of the gingiva revealed sheet-like proliferation of myeloperoxidase and CD45-positive large cells, and she was diagnosed with granulocytic sarcoma. Two years later, bone marrow involvement of granulocytic sarcoma was suspected. Her chromosome study repeatedly revealed a 46,XX,t(5;12)(q13;p13) karyotype. Case reports of t(5;12)(q13;p13) are extremely rare in the literature. To our knowledge, this is the first report of t(5;12)(q13;p13) in a patient with acute myelogenous leukemia with preceding granulocytic sarcoma.     

Disruption of the ETV6 gene as a consequence of a rare translocation (12;12)(p13;q13) in treatment-induced acute myeloid leukemia after breast cancer

We describe a case of treatment-induced acute myeloid leukemia M2 after breast cancer with a rare reciprocal t(12;12)(p13;q13) as a secondary cytogenetic abnormality in addition to the t(11;19)(q23;p13.1). Fluorescence in situ hybridization analysis revealed that both ETV6 genes (previously TEL) were located on the same der(12)t(12;12) as a result of t(12;12). Interestingly, the translocated ETV6 gene was disrupted, indicating the breakpoint on the large der(12)t(12;12) to be within the ETV6 gene and thus the possible formation of a new fusion gene. CHOP gene at 12q13, was found to be translocated intact to the other homologue chromosome 12, indicating that the breakpoint on the small der(12) is proximal to CHOP. To the best of our knowledge, our patient represents the first report of the rare t(12;12)(p13;q13) described in treatment-induced leukemia and the possible formation of a new fusion gene.     

Novel clonal der(8)t(8;14)(p11;q11),del(9)(q13q22) and t(14;22) (q13;q13) in a patient with fulminant adult T-cell leukemia/lymphoma

We describe a 70-year-old man with fulminant adult T-cell leukemia/lymphoma. He died of progressive disease 1 week after the onset of symptoms. The integrated viral DNA of human T-lymphotropic virus type I was detected in the bone marrow aspirate by polymerase chain reaction. Cytogenetic analysis of bone marrow cells showed novel clonal aberrations consisting of 46,XY,der(8)t(8;14)(p11;q11),del(9) (q13q22),t(14;22)(q13;q13).     

Localization of the chromosome 22 breakpoints in two cases of acute megakaryoblastic leukemia with t(1;22)(p13;q13)

We describe a 54-year-old man with CD2, CD7, and CD56-positive but CD3, CD4, and CD8-negative aggressive NK cell lymphoma/leukemia. Chromosome analysis of the peripheral blood cells showed clonal aberration consisting of 46,XY,dup(3)(p21p25),der(3)t(1;3)(q12;p25),del(5)(q13q22), del(6)(q13),del(13)(q12q14). The peripheral blood lymphoma cells contained clonal EBV-DNA by Southern blot analysis. The disease was refractory to chemotherapy and the clinical course was aggressive and rapid. Deletion 6q and deletion 13q have been frequently reported in NK cell lymphoma/leukemia. Thus, some tumor suppressor genes involving NK cell malignancies may be present in these regions.     

Precursor T-lymphoblastic leukemia with a novel t(1;22)(p34;q13)

A 37-year-old woman that presented with cervical lymphadenopathy and leukocytosis was found to have precursor T-lymphoblastic leukemia (T-ALL). Cytogenetic study of the leukemic cells showed a 46,XX, t(1;22)(p34;q13) karyotype. The t(1;22)(p34;q13) is a novel chromosomal abnormality in human malignancies and is probably a variant form of the t(1;14)(p34;q11) found in precursor T-ALL.     

Translocation (2;8)(p12;q24) associated with a cryptic t(12;21)(p13;q22) TEL/AML1 gene rearrangement in a child with acute lymphoblastic leukemia

We report a case of childhood acute lymphoblastic leukemia with the simultaneous occurrence of a t(2;8)(p12;q24) typically associated with mature B cell or Burkitt leukemia, and a t(12;21)(p13;q22) exclusively associated with pre-B cell ALL. The lymphoblasts were characterized as L2 morphology by the French-American-British classification. However, there were atypical morphologic findings for L2 ALL, including vacuolization in some cells. The lymphoblasts were periodic acid-Schiff positive and myeloperoxidase negative. Immunophenotypic analysis revealed that the majority of lymphoblasts were TdT+, CD10+, CD19+, CD20-, and cytoplasmic mu+. These features were consistent with an immature pre-B cell leukemia phenotype with some characteristics of a mature B-cell leukemia. A t(2;8)(p12;q24)(p12;q24), characteristic of mature B-cell leukemia or Burkitt type leukemia, was detected by conventional cytogenetics with no other cytogenetic abnormalities. However, diagnostic peripheral blood and bone marrow specimens demonstrated simultaneous occurrence of a cryptic t(12;21)(p13;q22) by both FISH and RT-PCR. The simultaneous occurrence of these translocations in a pediatric patient have implications for the pathogenesis of leukemias with t(2;8)(p12;q24) as well as t(12;21)(p12;q22). Analysis of additional cases of leukemia with translocations involving the MYC locus on 8q24 will be required to determine the frequency of association with the cryptic t(12;21)(p13;22), and the prognostic significance of the simultaneous occurrence of the translocations.     

Hu-ets-1 gene in congenital leukemia with t(11;19)(q23;p13)

Cytogenetic analysis of the leukemic cells from a 1-day-old baby with an acute myelomonocytic leukemia revealed them to contain a chromosome change of t(11;19)(q23;p13). Molecular studies using a 980 bp HindIII/HpaI digested v-ets probe showed no DNA rearrangements, deletions, or amplification in the leukemic cells, including the JH immunoglobulin and T-cell receptor ( or β) genes. The findings indicate that the leukemic cells with t(11;19)(q23;p13) appear not to contain a transposition or rearrangement of the protooncogene Hu-ets-1 located at 11q23, as previously described in leukemic cells with t(4;11)(q21;q23) and t(9;11)(p22;q23). The leukemic cases with t(11;19)(q23;p13) studied by us showed a phenotype compatible with their myelomonocytic nature, although it is possible that other cases may have a lymphoid phenotype.     

Unbalanced translocation der(11)t(11;12)(q23;q13): a new recurrent cytogenetic aberration in myelodysplastic syndrome with a complex karyotype

Cytogenetic abnormalities are observed in approximately one half of cases of myelodysplastic syndrome (MDS). Partial or complete chromosome losses and chromosome gains are frequently found, but there is a relatively high incidence of unbalanced translocations in MDS. We describe here two cases of MDS with an unbalanced translocation, der(11)t(11;12)(q23;q13). Both patients were 69 years of age and diagnosed with refractory anemia with excess of blasts in transformation (RAEB-t) according to the high percentage of blasts in the peripheral blood. Cytoplasmic hypogranulation of neutrophils was evident as a dysplastic change. The blasts were positive for CD4 and CD41a as well as CD13, CD33, CD34 and HLA-DR in both cases. Chromosome analysis showed complex karyotypes including a der(11)t(1;11)(q11;p15)t(11;12)(q23;q13) in case 1 and der(11)t(11;12)(q23;q13) in case 2 plus several marker chromosomes. Spectral karyotyping confirmed the der(11)t(11; 12)(q23;q13) and clarified the origin of marker chromosomes, resulting in del(5q) and del(7q). Fluorescence in situ hybridization (FISH) analyses with a probe for the MLL gene demonstrated that the breakpoints at 11q23 were telomeric to the MLL gene in both cases. FISH also showed that the breakpoint at 11p15 of the case 1 was telomeric to the NUP98 gene. Considering another reported case, our results indicate that the der(11)t(11;12)(q23;q13) is a recurrent cytogenetic abnormality and may be involved in the pathogenesis of advanced-stage MDS.     

Characterization of t(11;19)(q23;p13.3) by fluorescence in situ hybridization analysis in a pediatric patient with therapy-related acute myelogenous leukemia

This case presents a Caucasian girl diagnosed with early pre-B cell acute lymphoblastic leukemia at age 2 years. The only chromosomal anomaly detected in her bone marrow cells at this time was an add(12p). By age 4 years, she had a bone marrow and central nervous system (CNS) relapse of ALL and was treated with chemotherapy that included etoposide. She was in complete remission for 2 years following chemotherapy with etoposide, but later developed therapy-related acute myeloid leukemia (t-AML). At this time, a t(11;19)(q23;p13.3) rearrangement was detected in her bone marrow cells. The AML relapsed again 1 year after allogeneic bone marrow transplant (BMT). The presence of a chromosome 11 abnormality involving band 11q23 in this patient suggests that the transformation from ALL to t-AML was a consequence of etoposide included in her chemotherapy. Studies have shown that the 11q23 breakpoint in the t(11;19) rearrangement is consistent, and involves the MLL gene in t-AML patients. However, the breakpoint in 19p is variable in that it could be located either at 19p13.1 or 19p13.3 and thus could involve either of two genes: ELL (11-19 lysine-rich leukemia gene) on 19p13.1 or ENL (11-19 leukemia gene) on 19p13.3. In this study, the t(11;19)(q23;p13.3) was further characterized and the breakpoint regions were defined by fluorescence in situ hybridization (FISH) analysis.     

Therapy-related acute leukemia with mixed phenotype and t(9;22)(q32;q11.2): a case report and review of the literature

Therapy-related acute leukemia showing mixed phenotype is extremely rare. We report a 49-year-old woman who presented with palpable masses in her neck and back. She had received systemic chemotherapy (adriamycin and cisplatin) and radiotherapy for endometrial adenocarcinoma 7 years before. Her peripheral blood and bone marrow showed increased blasts, which coexpressed myeloid (CD13, CD33, and myeloperoxidase) and B-lymphoid antigens (CD19 and CD79a). Cytogenetic analysis showed a karyotype of 46,XX,dup(1)(q21q32),add(5)(q33),t(9;22)(q34;q11.2)[12]/47,idem,+der(22)t(9;22)[8], and BCR/ABL1 rearrangement was detected. Leukemic infiltration was also confirmed in her back mass. After induction chemotherapy with idarubicin, cytarabine, and imatinib, she achieved complete remission. Only 2 cases of therapy-related acute leukemia with mixed phenotype have been reported so far: one with hyperploidy and the other with t(1;21)(p36;q22). To the best of our knowledge, this is the first case of therapy-related acute leukemia with mixed phenotype and t(9;22) as well as extramedullary leukemic infiltrations.     

A der(13)t(7;13)(p13;q14) with monoallelic loss of RB1 and D13S319 in myelodysplastic syndrome

Deletions or translocations of chromosome band 13q14, the locus of the retinoblastoma gene (RB1), have been observed in a variety of hematological malignancies including myelodysplastic syndrome (MDS). We describe here a novel unbalanced translocation der(13)t(7;13)(p13;q14) involving 13q14 in a patient with MDS. A 66-year-old woman was diagnosed as having MDS, refractory anemia with excess of blasts (RAEB-1) because of 7.4% blasts and trilineage dysplasia in the bone marrow cells. G-banding and spectral karyotyping analyses showed complex karyotypes as follows: 46,XX,der(6)t(6;7)(q11;?),der(7)del(7)(?p13)t(6;7)(q?;q11)t(6;13)(q?;q?),der(13)t(7;13)(p13;q14). Fluorescence in situ hybridization (FISH) analyses demonstrated that one allele of the RB1 gene and the microsatellite locus D13S319, located at 13q14 and telomeric to the RB1 gene, was deleted. Considering other reported cases, our results indicate that submicroscopic deletions accompanying 13q14 translocations are recurrent cytogenetic aberrations in MDS. The RB1 gene or another tumor suppressor gene in the vicinity of D13S319, or both, may be involved in the pathogenesis of MDS with 13q14 translocations by monoallelic deletion.     

Translocation t(4;11)(q35;p13) in an adrenocortical carcinoma

Chromosome studies were performed on an adrenocortical carcinoma extending into the kidney. The following karyotype was present in all metaphases: 46,XX,t(4;11)(q35;p13). Two metaphases with an additional del(1)(q23) were found. The results are briefly discussed in relation to specific karyotypic changes in cancer, in general, and to those of adrenocortical tumors, in particular.     

Spontaneous expression of fra(11)(q23) in a patient with Ewing's sarcoma and t(11;22)(q23;q11)

Cytogenetic analysis of a Ewing's sarcoma revealed a 46,XX,t(8;18)(q11;q21.3), t(11;22)(q23–24;q11–12) chromosome pattern. Observation of t(11;22) is consistent with other reported cases of Ewing's sarcoma. One breakpoint in this translocation, 11q23, coincides with the location of a folate-sensitive fragile site. Examination of peripheral blood leukocyte chromosomes from the patient revealed a 46,XX chromosome pattern with spontaneous, fluorodeoxyuridine-, and Bactrim-induced expression of fra(11)(q23). This may be the first demonstration of constitutional fra(11)(q23) expression in a patient with a neoplasm that exhibits a chromosome rearrangement involving this breakpoint and the first observation of spontaneous expression of this fragile site. These results provide a basis for discussion of the relationship between fragile sites and chromosome rearrangements.     

Trisomy 18q: 46, XX,13q+,t(13;18)(q32;q11) in a newborn associated with multiple congenital anomalies due to paternal reciprocal translocation, 46, XY,-13,+der(13)/t(13;18)(q32;q11)

A 20-day-old female neonate presented with multiple congenital anomalies, convulsions and failure to thrive. Karyotype analysis of the proposita revealed an unbalanced translocation, 46, XX,13q+,t(13;18)(q32;qll)pat resulting in partial trisomy 18q. Her father and a 5-year-old sister were phenotypically normal, balanced translocation carriers, 46, XY, -13, + der(13),t(13;18)(q32;qll) and 46, XX,-13,+der(13),t(13;18)(q32;qll), respectively. The case presented here is the second liveborn reported with trisomy 18q and is of interest from the point of view of the structural chromosomal aberration resulting in the manifestations of most features of trisomy 18 and some of 13q monosomy. The infant died due to convulsions at the age of 2 months.     

Multiple apparently unrelated clonal chromosome abnormalities in a squamous cell carcinoma of the tongue

We have cytogenetically examined short-term cultures from a squamous cell carcinoma of the tongue, a tumor type in which chromosome aberrations hitherto have not been reported. No less than 12 pseudodiploid clones were detected, giving the tumor karyotype 46,X,der(X)t(X;1)(q26;p32),der(1)(Xqter→Xq26::1p32→cen→1q42:),del(13)(q11q21),t(15;?) (q26;?)/46,XX,t(1;?)(p34;?),inv(2)(p21q11)/46,XX,t(1;10)(p32;q24)/46,XX,+der(1)(12pter→ 12p11::1p11→cen→1q32::11q13→11q32→1q42:),del(11)(q13q22), - 12, der(17)t(1:17) (q42;p13)/46,XX,inv(1)(p22q44)/47,XX,del(1)(q32),der(17)t(1:17)(p22;q25),der(1)inv(1) (q25q44)t(1;17)(p22;q25),ins(14;7)(q11;q22q36), + 14/46,XX,t(1;4)(q23;q35)/46,XX,t(1;21) (q25;q22),t(2;10)(q31;q26),t(22;?)(q12;?)/46,XX,del(1)(q32)/46,XX,t(1;8)(q44;q21)/46,XX, t(2;21)(q11;p11)/46,XX,t(9;11)(q34;q13). The large number of apparently unrelated abnormalities leads us to suggest that the carcinoma may have been of multiclonal origin.     

Translocation t(1;19)(q23;p13) in acute lymphoblastic leukemia. A report on six new cases and an unusual t(17;19)(q11;q13), with special reference to prognostic factors

We report clinical, immunologic, and cytogenetic characteristics of six patients with a t(1;19)(q23;p13) that was balanced in one case and of the unbalanced type [-19,der(19)t(1;19)(q23;p13)] in the remaining five cases. Intracytoplasmic immunoglobulins (cIg) were positive in the three cases where they were found. We also report on another patient, with a t(17;19) involving 17q11 and probably 19q13 regions, although involvement of 19p13 could not be excluded. In this patient, cIg were also present, thus raising the issue of whether such a rearrangement could be a variant of t(1;19). Clinically, five patients belonged to the high-risk acute lymphoblastic leukemia (ALL) group, because of high leukocytosis, central nervous system (CNS) disease at presentation, or massive organomegaly. Cytologically, all cases were FAB type L1. Except for the two cases allografted in the first complete remission (CR) all patients relapsed, three of them within 13 months. Two CNS relapses were seen in spite of adequate CNS prophylaxis. ALL with t(1;19) appears to be a poor-risk ALL subgroup and probably requires a reinforcement of therapeutic modalities that might include, when possible, allografting at first CR.     

Therapy-related, mixed phenotype acute leukemia with t(1;21)(p36;q22) and RUNX1 rearrangement

We describe here a new case of therapy-related acute leukemia with t(1;21)(p36;q22). A 25-year-old man was admitted because of anemia and thrombocytopenia. Four years before, he had received combination chemotherapy including etoposide for seminoma. Bone marrow was hypercellular, with 49% myeloperoxidase (MPO) staining-negative blasts. Chromosome analysis showed 46,XY,t(1;21)(p36.3;q22)[11]/49,sl,+8,+16,+20[9]. Fluorescence in situ hybridization demonstrated that RUNX1 signals at 21q22 were split onto the der(1)t(1;21) and der(21)t(1;21). Immunophenotypic analyses revealed that blasts were positive for CD19, CD79a, and cytCD22, as well as MPO, CD13, and CD33, fulfilling the diagnostic criteria of mixed phenotype acute leukemia, B/myeloid. The patient died of disease progression after 10 months. Thus, acute leukemia with t(1;21) and RUNX1 rearrangement could be associated with B/myeloid mixed phenotype as well as previous topoisomerase II inhibitor therapy and poor prognoses.     

Monosomy 10qter due to a balanced maternal translocation: t(10;8)(q23;p23)

A new case of partial monosomy 10q is described. The clinical symptoms are similar to the previous cases reported, although the segment lost is larger (q23-qter). The mother was a balanced carrier of 46,XX,t(10;8)(q23;p23). Amniocentesis was carried out since the mother was again pregnant and the result was a female fetus 46,XX,t(10;8)(q23;p23).