Unusual Cytogenetic Findings Research Articles

A Rare Case of Acute Promyelocytic Leukemia with Concomitant PML-RARA Fusion and TP53 Loss/ider(17)(q10)t(15;17) Showing Complete Clinical and Molecular response: A Case Report

Abstract Introduction/Objective To report a case with rare cytogenetic abnormality: a patient with newly diagnosed acute promyelocytic leukemia (APL) with cytogenetic findings of t(15;17)(q24;q21), trisomy 8 and ider(17)(q10)t(15;17)-TP53 loss. The presence of isochromosome 17q may indicate the possibility of an unfavorable outcome. However, the case showed complete clinical and molecular response. Methods/Case Report A case of a 53-year-old female with history of ITP post-splenectomy presented with persistent hematuria, easy bruising, and worsening fatigue. She had mild microcytic anemia, moderate thrombocytopenia, 3% promyelocytes, and 14% blasts on differential CBC count. With increased PT, PTT, LDH, Uric acid and decreased fibrinogen level, APL was clinically suspected. The patient was initiated on all-trans retinoic acid (ATRA), allopurinol, and IV fluids. Bone marrow (BM) biopsy confirmed the diagnosis with unusual cytogenetic findings. The patient underwent induction and consolidation therapies (4 weeks each) with ATRA plus Arsenic Trioxide (ATO) and followed- up with a series of marrow biopsies, cytogenetic and molecular studies. Results (if a Case Study enter NA) The patient demonstrated complete clinical, histological, and molecular response. She tolerated the treatment without major side effects, showing improvement in CBC counts, coagulation profile and tumor lysis labs. Initial BM exam revealed hypercellularity with infiltrating sheets of atypical hypergranular promyelocytes (~80%) and minimal residual left trilineage hematopoiesis. Flow cytometry revealed a CD34 negative, CD117 variable abnormal promyelocyte population (~67% of total events). FISH was positive for PML/RARA translocation (15; 17) and TP53 loss. Karyotype showed 46,XX,der(15)t(15;17)(q24;q21),ider(17)(q10)t(15;17)[12]/47,idem,+8[9]. By the end of treatment, BM biopsy was normocellular with trilineage hematopoiesis and no definitive evidence of acute leukemia or increase in blasts. The Karyotype was normal. Quantitative PCR for PML-RARA was negative, indicating complete molecular remission. Conclusion In this unique case of APL with unusual cytogenetic abnormalities the literature demonstrates controversial data. The patient achieved complete clinical and molecular remission following standard treatment. This may indicate the limited prognostic significance of these additional cytogenetic abnormalities in this case.

Unusual Genetic Aberrations Including a Deletion of KLF6 Tumor Suppressor Gene Revealed by Integrated Cytogenetic Approaches in a Pediatric Ewing Sarcoma

Ewing sarcoma is the third most common sarcoma in children and young adults. Its characteristic chromosomal rearrangement results in a chimerical EWSR1-ETS transcription factor. Secondary genetic alterations are very common. Membranous expression of CD99 is seen in almost all tumors. We report 2 unusual cytogenetic findings in a pediatric Ewing sarcoma, an insertion of the MIC2 gene encoding CD99 from Xp to 10p and a submicroscopic deletion of the well-known tumor supressor gene KLF6. The latter has not been described previously in pediatric neoplasms. Molecular pathways in tumorigenesis and genetic complexity in cancer are discussed.

An Indolent Case of T-Prolymphocytic Leukemia With t(3;22)(q21;q11.2) and Elevated Serum β2-Microglobulin

Abstract We report a novel case of T-prolymphocytic leukemia, small cell variant, associated with complex cytogenetic findings including t(3;22)(q21;11.2) and elevated serum β2-microglobulin. The diagnosis is based on morphologic, immunophenotypic, cytogenetic, and molecular analysis of peripheral blood and bone marrow. In contrast to most reported cases of T-prolymphocytic leukemia, this patient did not present with lymphadenopathy or organomegaly. Moreover, only a moderate leukocytosis (25.3 × 103/μL) was evident at presentation. In the absence of any specific treatment, the patient is doing well, with a stable white blood cell count 12 months following presentation. Further investigation may be warranted to determine whether the unusual cytogenetic findings and elevated serum β2-microglobulin are associated with the indolent clinical course in this patient.

Unusual cytogenetic findings in a synovial sarcoma arising in the paranasal sinuses

A fresh specimen from an intracranial tumor, which was histopatologically classified as a synovial sarcoma, was investigated cytogenetically. The direct method failed to give any information due to a lack of mitotic cells after treatment with 70% acetic acid, whereas 6-day cultures showed a 45,XY,del(6q),-10 karyotype. The histologic evaluation was consistent with a synovial sarcoma, which is well characterized from a cytogenetic perspective and involves a t(X;18)(p11;q11) in more than 95% of cases. Reverse-transcription polymerase chain reaction analysis did not show the presence of the SYT-SSX chimeric gene.

Uncommon karyotypic abnormality, t(11;19)(q23;p13.3), in a patient with blastic phase of chronic myeloid leukemia

We describe unusual cytogenetic findings in a 33-year-old male with blastic phase of Philadelphia chromosome (Ph)-positive chronic myeloid leukemia. In addition to the t(9;22)(q34;q11), which was detected in all metaphases, a t(11;19)(q23;p13.3) was also identified as an evolutional change in all 20 metaphases. Fluorescence in situ hybridization (FISH) analysis showed that fusion signals of the ABL/BCR probes were found in 95% of blastic cells. Southern blotting and FISH analysis also revealed involvement of the MLL gene on 11q23. Clinical course was aggressive and the patient responded poorly to therapy. These findings suggest an association between Ph and 11q23 with poor prognosis, and that t(11;19)(q23;p13.3) was the essential pathogenic factor in our case.

Unusual chromosomal mosaicism in Wolf-Hirschhorn syndrome: del(4)(p16)/der(4)(qter-q31.3::pter-qter)

We report on the unusual cytogenetic findings in a girl with moderate mental retardation and a mosaic karyotype 46,XX,del(4)(p16)/46,XX,der(4)(qter-q31.3::pter-qter). The facial features observed in the child initially did not suggest the diagnosis of Wolf-Hirschhorn syndrome (WHS), but the distinct facial gestalt became obvious at prepubertal age. Fluorescence in situ hybridization (FISH) analysis with different probes that map to 4p and 4q helped to clarify the karyotype. We discuss the mechanism of appearance of this unusual type of mosaicism, which has not been reported before.

Fetoplacental chromosomal discrepancy

Chorionic villus sampling is now an acceptable alternative to second trimester amniocentesis. Several reports have raised concerns about the occurrence of discrepancies between the chorionic villi and fetal chromosomal constitution, which adds multiple diagnostic complexities to the process of prenatal genetic counselling. We report on a series of 26 cases in which fetoplacental discrepancies have occurred. The chromosomal aberration was exclusively confined to the placenta in 21 cases. Twice the identical aberration was also observed in amniotic fluid with variant range of aneuploidy. The chromosomal abnormality was found in amniotic fluid and fetal blood samples in two cases, and was absent in chorionic villi. One case had very unusual cytogenetic findings as two different non-mosaic chromosomal abnormalities were identified separately in the placenta and amniocytes. Among the 21 gestations with confined placental abnormal karyotype, three cases of intrauterine growth retardation were identified. Of six cases evaluated for uniparental disomy, four demonstrated biparental inheritance. These findings support a positive correlation between placental aneuploidy and abnormal fetal development. They also emphasize the importance of further DNA analysis whenever discrepant karyotype findings between the placenta and amniocytes are identified.

Cytogenetic heterogeneity in blast crisis (BC) of chronic myelogenous leukemia (CML)

New cytogenetic findings are reported in a patient who entered into an accelerated blastic phase of chronic myelogenous leukemia (CML). The cytogenetic findings of this case can be described as 46, xy, t (5;7) (q 31;q 11), t (9;22) (q 34;q 11), Ph'. The prognostic implications in such patients with rare and unusual cytogenetic findings are discussed.

Translocation X;10 in a case of congenital acute monocytic leukemia

Unusual cytogenetic findings were noted in the leukemic cells from a patient with congenital acute monocytic leukemia (AMol or M5, according to the FAB classification), whereas, the chromosomes of cultured skin fibroblasts were normal. G-banded karyotypes of leukemic cells showed an X-autosome translocation, 46,X,t(X;10) (Xpter→q13::10q11.2→qter)(10pter→q11.2::Xq28→q13:: Xq28→qter). Review of reported cases of acute nonlymphocytic leukemia (ANLL) with rearrangements involving chromosomes #10 or X showed a high frequency of abnormalities of the short arm of #10 in myelomonocytic (M4) and monocytic (M5) leukemias, particularly in patients less than 2-yr-of-age. Although previously reported cases of ANLL in infants are predominantly of these types, the translocation observed in this case is unique. Fragile sites known to exist on chromosomes #10 and X are not associated with neoplasia and, except for Xq27–28, were not at the breakpoints of the case presented. The precise location of a human cellular oncogene recently identified on the X chromosome remains unknown.

Translocation 4;11 acute leukemia: Three case reports and review of the literature

Three children with acute leukemia and t(4;11)(q21;q23) are presented. Two of the cases showed very unusual karyotypic findings and long survival for the type of leukemia. In case B.T., the original karyotype change observed was t(4;11), with other changes (+4q−,+11q+,+6,+10) appearing during the last stages of the disease. In case R.B., the translocation was accompanied by many numerical and morphological chromosome changes, with a near-tetraploid chromosome number. In both of the above cases, remission was associated with a normal marrow karyotype. In case D.C., only the t(4;11) was observed. The number of cases with t(4;11) and acute leukemia published so far is 36, including the three cases presented by us. As this disease is usually characterized by a relatively short survival, the possible reasons for the remarkably long survival in two of our patients are discussed in relation to the rather unusual cytogenetic findings.

Chromosomes and causation of human cancer and leukemia. XXXIV. A case of “hypereosinophilic syndrome” with unusual cytogenetic findings in a chloroma, terminating in blastic transformation and CNS leukemia

A 47-year-old white male developed massive hepatosplenomegaly, a pleural effusion, leucocytosis, and a left parasternal mass following a relatively symptom-free persistent hypereosinophilia for about 5 years. Bone marrow aspiration and biopsy and peripheral blood differential showed eosinophilia and a shift to the left with immature cells. A high serum B12 vitamin level and low LAP activity were found. Biopsy of the soft tissue mass revealed a granulocytic sarcoma (chloroma) with a hyperdiploid karyotype (49,XY, + 10, + 15, + 19,3q-), whereas the bone marrow cells had a normal male karyotype. The patient responded temporarily to chemotherapy but eventually developed CNS leukemia and went on to terminate in a frank blastic phase. This case illustrates hypereosinophilia and a myeloproliferative syndrome characterized by a somewhat indolent chronic course evolving into "eosinophilic leukemia" and granulocytic sarcoma, CNS involvement by leukemic cells and, finally, blastic transformation. It is possible that this case represents a variant of Ph1-negative CML to which the term "chronic eosinophilic leukemia" could be justifiably applied.

Cytogenetic Remission in a Ph1‐Positive Case of Chronic Myelogenous Leukaemia

Unusual cytogenetic findings in a case of chronic myelogenous leukaemia in the course of an aplastic crisis induced by busulfan therapy are reported. The proportion of Ph1-positive cells in bone marrow aspirates fell from 100% before treatment to 8.6% following aplasia. It increased gradually during recovery, and normal cells still represented 25.7% of the metaphases 20 months later. After a 38-months' remission without therapy the disease relapsed and the Ph1 chromosome was found in 100% of the bone marrow cells.