Translocations leading to fusions between the immunoglobulin heavy chain gene (IGH) and various partner genes have been reported in B-cell precursor acute lymphoblastic leukemia (B-ALL). However, submicroscopic deletions within IGH in B-ALL have not been rigorously assessed. In this study, we investigated characteristics of IGH submicroscopic deletions, by FISH, in B-ALL with IGH rearrangements. FISH was performed by using commercially available IGH dual-color break-apart rearrangement probes (Abbott/Vysis, Downers Grove, IL, USA; Kreatech, Amsterdam, Netherlands). The study group included seven B-ALL patients with IGH rearrangements, observed by FISH. Among them, two exhibited deletion of the 5' variable region of IGH by FISH. The B-ALL in these two patients included two kinds of abnormal cells; one had an IGH rearrangement without any IGH submicroscopic deletion, while the other had an IGH submicroscopic deletion, which showed that one normal fusion signal and one 3' IGH signal were detected. Thus, submicroscopic deletion of the IGH 5' variable region may have occurred in either the native or rearranged chromosome 14. These findings indicate that B-ALL with IGH rearrangements may be accompanied by submicroscopic deletions of the IGH 5' variable region, which can be detected by FISH. The clinical significance of such deletions is unclear, but the loss of part of the IGH gene in B-ALL warrants further study.
Adult ; Child ; Female ; *Gene Deletion ; *Gene Rearrangement ; Humans ; Immunoglobulin Heavy Chains/*genetics ; In Situ Hybridization, Fluorescence ; Infant ; Male ; Middle Aged ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/*genetics/pathology ; Young Adult

Acute sprain of the ankle requires comprehensive history taking and physical examination in diagnosing the type of severity and deciding on the plan of treatment. Literature supports functional treatment as the treatment of choice for grade I and II injuries. During the acute phase, the goal of treatment focuses on controlling pain and swelling. PRICE (protection, rest, ice, compression, and elevation) is a well-established protocol at this phase. There is some evidence that application of ice and use of nonsteroidal anti-inflammatory drugs improves healing and speeds recovery. Then the functional treatment (motion restoration and strengthening exercises) is administered to progress the rehabilitation appropriately in order to facilitate healing and restore the mechanical strength and proprioception. Early mobilization has been shown to result in more rapid return to work and daily activities than immobilization. Grade III injuries still generate controversy in terms of the best management available, and more studies on early mobilization, cast immobilization, or surgery are needed. Even the Cochrane reviews published to date are not conclusive.
Ankle Injuries* ; Ankle* ; Diagnosis* ; Early Ambulation ; Ice ; Immobilization ; Physical Examination ; Proprioception ; Rehabilitation ; Return to Work ; Sprains and Strains

A genomic instability called chromothripsis occurs as a single catastrophic event, generating massive complex genomic rearrangement with a possible characteristic pattern of copy number oscillations. Here, we report a case of secondary plasma cell leukaemia (PCL) showing chromothripsis identified by single nucleotide polymorphism array (SNP-A)-based karyotyping. A 53-year-old male patient was diagnosed as having secondary PCL four years after he was diagnosed with multiple myeloma, and he died four days later due to intracerebral haemorrhage. Chromosomal analysis and fluorescence in situ hybridization (FISH) revealed the deletions of 13q and 17p and an insertion of 1q. Further, genomic aberrations that were not detected by chromosomal analysis and FISH were identified by SNP-A. In particular, SNP-A revealed numerous alternating copy number state switches involving one, two, or three copy number states on chromosome 7q, suggesting the presence of chromothripsis. The present case suggests that chromothripsis may occur in secondary PCL and can be inferred from genomic copy number profiles identified by SNP-A.
Fluorescence ; Genomic Instability ; Humans ; In Situ Hybridization ; Karyotyping ; Male ; Middle Aged ; Multiple Myeloma ; Plasma Cells* ; Polymorphism, Single Nucleotide

Prognosis is known to be better in cases with isolated chromosomal abnormalities than in those with complex karyotypes. Accordingly, del(20q) as an isolated abnormality must be distinguished from cases in which it is associated with other chromosomal rearrangements for a better stratification of prognosis. We report a case of an isolated del(20q) abnormality with additional genomic aberrations identified using whole-genome single nucleotide polymorphism array (SNP-A)-based karyotyping. A 39-yr-old man was diagnosed with AML without maturation. Metaphase cytogenetic analysis (MC) revealed del(20)(q11.2) as the isolated abnormality in 100% of metaphase cells analyzed, and FISH analysis using D20S108 confirmed the 20q deletion in 99% of interphase cells. Using FISH, other rearrangements such as BCR/ABL1, RUNX1/RUNX1T1, PML/RARA, CBFB/MYH11, and MLL were found to be negative. SNP-A identified an additional copy neutral loss of heterozygosity (CN-LOH) in the 11q13.1-q25 region. Furthermore, SNP-A allowed for a more precise definition of the breakpoints of the 20q deletion (20q11.22-q13.31). Unexpectedly, the terminal regions showed gain on chromosome 20q. The patient did not achieve complete remission; 8 months later, he died from complications of leukemic cell infiltrations into the central nervous system. This study suggests that a presumably isolated chromosomal abnormality by MC may have additional genomic aberrations, including CN-LOH, which could be associated with a poor prognosis. SNP-A-based karyotyping may be helpful for distinguishing true isolated cases from cases in combination with additional genomic aberrations not detected by MC.

Cases of clonal cytogenetic abnormalities in Philadelphia-negative cells during the treatment of Philadelphia-positive CML have been previously reported. However, clonal abnormalities unrelated to the original t(8;21) or t(15;17) karyotype are not common. Deletion of 20q (del(20q)) is one of the most common recurrent cytogenetic abnormalities in myeloid neoplasms. Here we describe 3 patients with t(8;21), t(15;17), or t(9;22) who developed unrelated del(20q) after successful treatment of leukemia. We retrospectively reviewed the cytogenetic results of 23 AML patients with t(8;21)(q22;q22), 28 AML patients with t(15;17)(q22;q12), and 47 CML patients with t(9;22)(q34;q11.2). We identified 3 patients with del(20q) as the only clonal aberration unrelated to the primary karyotype when they achieved complete morphologic and cytogenetic remission. The latency period between diagnosis and emergence of del(20q) was 1, 114, and 35 months for the 3 patients, respectively. There was no evidence of therapy-related MDS/AML during the follow-up period. In 1 AML patient with t(8;21), relapse occurred in a t(8;21)(q22;q22) clone and the del(20q) clones were lost. The clinical significance of del(20q) as an unrelated clonal aberration is unknown, but our study suggests that del(20q) does not cause therapy-related MDS/AML or indicate disease progression.
Chromosome Aberrations ; Chromosome Deletion ; Chromosomes, Human, Pair 20 ; Clone Cells ; Cytogenetics ; Disease Progression ; Follow-Up Studies ; Humans ; Karyotype ; Latency Period (Psychology) ; Leukemia ; Recurrence ; Retrospective Studies

Trisomy 22 is closely associated with inv(16) or t(16;16) and could be a marker of cryptic rearrangement of CBFB/MYH11 in acute myeloid leukemia (AML). Trisomy 22 not associated with CBFB/MYH11 rearrangement is a rare event. Here, we report a case diagnosed as refractory anemia with excess blasts-2 (RAEB-2) with sole trisomy 22 in the absence of CBFB/MYH11 rearrangement. The cytogenetic study of bone marrow cells disclosed trisomy 22 in 10% of metaphase cells analyzed. The other chromosomal abnormalities were not found. Fluorescence in situ hybridization (FISH) using CBFB/MYH11 probe to detect cryptic inv(16)(p13q22) showed negative result. We also excluded rearrangements of chromosome 5, 7, 8, 20, and ETV6 by FISH. Sole trisomy 22 not associated with inv(16) is a true entity.
Anemia, Refractory ; Bone Marrow Cells ; Chromosome Aberrations ; Chromosomes, Human, Pair 22 ; Chromosomes, Human, Pair 5 ; Cytogenetics ; Fluorescence ; In Situ Hybridization ; Leukemia, Myeloid, Acute ; Metaphase ; Myelodysplastic Syndromes ; Trisomy

Chromosomes forming a corresponding ring cannot be clearly defined by conventional cytogenetics or FISH. Karyotypic analyses using whole-genome single nucleotide polymorphism arrays (SNP-A) may result in the identification of previously cryptic lesions and allow for more precise definition of breakpoints. We describe a case of AML with metaphase cells bearing -5, del(11)(q22), and +r. With SNP-A, a 5p-terminal deletion (11 megabases [Mb]), a 5q-terminal deletion (27 Mb), an 11q-interstitial deletion (29 Mb), and a 21q gain (3 Mb) were identified. Therefore, the G-banded karyotype was revised as 46, XY, r(5)(p15. 2q33.2), del(11)(q14.1q23.2), dup(21)(q22.13q22.2)[18]/46,XY[2]. SNP-A could be a powerful tool for characterizing ring chromosomes in which the involved chromosomes or bands cannot be precisely identified by conventional cytogenetics or FISH.
Chromosome Deletion ; *Chromosomes, Human, Pair 5 ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Leukemia, Myeloid, Acute/*diagnosis/genetics ; Male ; Metaphase ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; *Polymorphism, Single Nucleotide ; *Ring Chromosomes

BACKGROUND: In patients with isolated thrombocytopenia, but without significant dysplasia, diagnosis of idiopathic thrombocytopenic purpura (ITP) rather than myelodysplastic syndrome (MDS) may be taken into account. It is important to make an accurate diagnosis because different treatments are used for ITP and MDS. The purpose of this study was to investigate the clinical and hematologic features of patients who were initially diagnosed as ITP but had cytogenetic abnormalities. METHODS: We retrospectively reviewed cytogenetic studies of 100 patients who were diagnosed as ITP from 2004 to 2009 at Mokdong Hospital of Ewha Womans University based on clinical features and hematologic studies. Bone marrow pathology was re-evaluated based on 2008 WHO classification. Cytogenetic analysis was performed by 24-48 hr culture of bone marrow aspirates without using mitogens and 20 metaphases were analyzed. RESULTS: Of the 100 patients diagnosed as ITP initially, three patients (3%) had cytogenetic abnormalities. They had no thrombocytopenia-related symptoms and thrombocytopenia was found accidentally. The numbers of megakaryocytes in bone marrow were increased and dysplasia was not found in megakaryocyte, erythroid, and myeloid cell lineages. The proportion of blasts was within normal limits. Clonal chromosomal abnormalities found were der(1;7)(q10;p10), add(9)(q12), or t(7;11)(p22;q12). Presumptive diagnosis of MDS or diagnosis of idiopathic cytopenia of undetermined significance (ICUS) was made according to 2008 WHO classification. During the follow up, disease progression was not found. CONCLUSIONS: In patients with suspected ITP, cytogenetic analysis should be done. If specific clonal chromosomal abnormality is found, presumptive diagnosis of MDS has to be considered and close follow up is needed.
Adult ; Bone Marrow Cells/cytology ; Cell Lineage ; Chromosome Aberrations ; Diagnosis, Differential ; Female ; Humans ; Male ; Megakaryocytes/immunology/pathology ; Middle Aged ; Myelodysplastic Syndromes/*diagnosis/genetics/pathology ; Purpura, Thrombocytopenic, Idiopathic/*diagnosis/genetics/pathology ; Retrospective Studies

PURPOSE: This study was designed to determine the quantitative changes of the numbers of the mechanoreceptors in the experimentally tenotomized Achilles tendon of rabbits as compared with short-term immobilization and long-term immobilization. MATERIALS AND METHODS: 14 white rabbits were used. After tenotomizing the right Achilles tendon, the subjects were divided into 2 groups according to the periods of immobilizaton. The left side of each Achilles tendon of the rabbits were used as controls. The tendons were stained with a modified gold-chloride method. RESULTS: The number of mechanoreceptor was significantly decreased in the tenotomized Achilles tendon group than the control group (p<0.01). There was no statistical difference between the two experimental groups in the numbers of the mechanoreceptors (p>0.01). CONCLUSION: The injured Achilles tendons may more vulnerable to injury because of the decreased numbers of mechanoreceptors, but no difference between the periods of immobilization. It may suggest that post-operative immobilization period may not affect on the outcome of operative treatment from the viewpoint of mechanoreceptors.
Achilles Tendon ; European Continental Ancestry Group ; Humans ; Immobilization ; Mechanoreceptors ; Rabbits ; Tendons

PURPOSE: This study was designed to determine the quantitative changes of the numbers of the mechanoreceptors in the experimentally tenotomized Achilles tendon of rabbits as compared with short-term immobilization and long-term immobilization. MATERIALS AND METHODS: 14 white rabbits were used. After tenotomizing the right Achilles tendon, the subjects were divided into 2 groups according to the periods of immobilizaton. The left side of each Achilles tendon of the rabbits were used as controls. The tendons were stained with a modified gold-chloride method. RESULTS: The number of mechanoreceptor was significantly decreased in the tenotomized Achilles tendon group than the control group (p<0.01). There was no statistical difference between the two experimental groups in the numbers of the mechanoreceptors (p>0.01). CONCLUSION: The injured Achilles tendons may more vulnerable to injury because of the decreased numbers of mechanoreceptors, but no difference between the periods of immobilization. It may suggest that post-operative immobilization period may not affect on the outcome of operative treatment from the viewpoint of mechanoreceptors.
Achilles Tendon ; European Continental Ancestry Group ; Humans ; Immobilization ; Mechanoreceptors ; Rabbits ; Tendons