Translocation (11;16)(q23;p13) acute myelogenous leukemia and myelodysplastic syndrome

The purpose of this study is to examine the relationship of t(11;16)(q23;p13) to the type of myeloproliferative disorder noted by hematopathology. Previously, t(11;16) has been reported in fewer than 20 patients, all with the diagnosis of therapy-related (secondary) acute myelogenous leukemia (sAML) or myelodysplastic syndrome (MDS). Putative involved genes are the MLL on 11q23 and CBP at 16p13. Data from The University of Texas M. D. Anderson Cancer Center (UTMDACC) Cytogenetics Laboratory revealed 3 patients with t(11;16) observed during the past 5 years. Two of the patients had a prior diagnosis of non-Hodgkin lymphoma (NHL) and had been treated with chemotherapy, which included cyclophosphamide. The other patient presented with de novo AML and no history of cancer or chemotherapy. Two of the 3 patients had t(11;16) as the sole cytogenetic abnormality. One patient had a t(11;16) clone that included t(9;21) and t(10;21) as additional changes. Translocation (11;16) has previously been reported only as being therapy-related. In this study, the t(11;16) was seen in 2 patients with previous lymphomas treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). A single patient with apparently de novo AML constitutes the first reported instance of non-treatment associated t(11;16) AML.     

Infant acute lymphoblastic leukemia with t(11;16)(q23;p13.3) and lineage switch into acute monoblastic leukemia

Rearrangements of the mixed-lineage leukemia (MLL) gene have been associated with a poor prognosis in infant acute lymphoblastic leukemia (ALL). Previously, MLL translocations involving the CREP-binding protein (CREBBP) gene at chromosome band 16p13.3 have primarily been reported in treatment-related acute myeloid leukemia, after chemotherapy for other primary malignancies using topoisomerase II inhibitors. We report a case of de novo infant ALL with t(11;16)(q23;p13.3). After chemotherapy, this patient developed an acute monoblastic leukemia (M5b) with retention of the t(11;16)(q23;p13.3), indicating that this is a lineage switch of the original leukemic clone. To our knowledge, these findings have not been previously reported.     

t(11;19)(q23;p11) in a child with acute T-cell leukemia

A translocation, t(11;19)(q23;p11), is reported in a child with T-cell leukemia. Our case indicates that the t(11;19) may not be restricted to the monocytic leukemias, as earlier reported, but may occur in other malignancies.     

Translocation (16;21)(p11;q22) in acute monoblastic leukemia with erythrophagocytosis

A patient with acute monoblastic leukemia with erythrophagocytosis and a t(16;21) (p11;q22), poor response to chemotherapy, early relapse, and a short survival of ten months is presented. Hematologically, this patient could be considered as a case of FAB M5b/t(8;16) but without the characteristic chromosomal translocation, i.e., there is no visible alteration on chromosome 8 and the breakpoint on chromosome 16 appears to be very proximal. These findings are briefly discussed in the light of other variants.     

A novel t(2;3)(q31;p13) in acute myelocytic leukemia

We report a case of acute myelocytic leukemia without maturation exhibiting a novel t(2;3)(q31;p13). Conventional cytogenetics showed the concomitant occurrence of a single metaphase with 47,XX,+8. Nevertheless, interphase cytogenetics by fluorescence in situ hybridization using a chromosome 8 alpha-satellite DNA probe showed that the percentage of cells with three hybridization signals was within the control range.     

t(9;11)(p22;q24) in a patient with acute monocytic leukemia

A case of t(9;11)(p22;q24) in a patient with acute monocytic leukemia is described. The difficulties of establishing the precise breakpoints involved in this emerging association are discussed.     

Translocation t(5;11)(q13.1;p13) associated with familial isolated aniridia

A father and daughter with isolated aniridia were observed to have an apparently balanced, reciprocal translocation involving chromosomes 5 and 11 [t(5;11)(q13.1;p13)]. No other clinical characteristics often associated with the deletion of 11p13 were observed in this family. This finding, in association with 3 other instances of single breaks at 11p13 and aniridia, supports the assignment of AN2 to 11p13.     

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.     

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.     

Reciprocal translocation (11;19)(q23;p13) in congenital acute lymphoblastic leukemia

The cytogenetic, clinical, and immunologic findings ina 4-month-old girl with acute lymphoblastic leukemia (ALL) are reported. The malignant lymphoblasts were characterized cytogenetically by the reciprocal translocation t(11;19)(q23;p13); immunologically by an immature pre-B-ALL phenotype. In spite of the high-risk nature of the leukemia, the patient attained complete remission relatively quickly and is still free of disease 3 years after diagnosis. Because the only two previously reported ALL patients with t(11;19) also seem to have responded well to therapy, this cytogenetic abnormality might turn out to be an indicator of favorable prognosis in ALL.