Acute myeloid leukemia (AML) is a phenotypically heterogeneous disorder. The M4 subtype of AML is frequently associated with the cytogenetic marker inversion 16 and/or the presence of eosinophilia. Blast crisis is the aggressive phase of the triphasic chronic myeloid leukemia (CML), which is a disease with Philadelphia(Ph) chromosome as the major abnormality. In the present study, we report a 76-year-old patient suspected of having AML with eosinophilic differentiation (AML-M4), which in clinical tests resembles CML blast crisis with multiple chromosomal abnormalities. Isochromosome 21 [i(21)(q10)] was the most recurrent feature noted in metaphases with 46 chromosomes. Ring chromosome, tetraploid endoreduplication, recurrent aneuploid clones with loss of X chromosome, monosomy 17, monosomy 7, and structural variation translocation (9;14) were also observed in this patient. Fluorescent in situ hybridization (FISH) confirmed the absence of Ph chromosome. This report shows how cytogenetic analyses revealed atypical structural aberrations in the M4 subtype of AML.
Aged ; Blast Crisis ; genetics ; Chromosome Aberrations ; Chromosome Deletion ; Chromosomes, Human, Pair 14 ; genetics ; Chromosomes, Human, Pair 17 ; genetics ; Chromosomes, Human, Pair 21 ; genetics ; Chromosomes, Human, Pair 7 ; genetics ; Chromosomes, Human, Pair 9 ; genetics ; Chromosomes, Human, X ; genetics ; Cytogenetic Analysis ; Endoreduplication ; Humans ; In Situ Hybridization, Fluorescence ; Isochromosomes ; Leukemia, Myelomonocytic, Acute ; genetics ; pathology ; Male ; Philadelphia Chromosome ; Polyploidy ; Ring Chromosomes ; Translocation, Genetic

OBJECTIVE: To explore the genetic basis for a rare case of acute B-lymphocytic leukemia (B-ALL) with double Philadelphia chromosomes (Ph) and double derivative chromosome 9s [der(9)]. METHODS: A patient with double Ph and double der(9) B-ALL who presented at Shanghai Zhaxin Intergrated Traditional Chinese and Western Medicine Hospital in June 2020 was selected as the subject. Bone marrow morphology, flow cytometry, G-banding karyotyping, fluorescence in situ hybridization (FISH), genetic testing and chromosomal microarray analysis (CMA) were used to analyze bone marrow samples from the patient at various stages. RESULTS: At initial diagnosis, the patient's bone marrow morphology and flow immunotyping have both supported the diagnosis of B-ALL. G-banded karyotyping of the patient indicated double Ph, in addition with hyperdiploid chromosomes involving translocations between chromosomes 9 and 22. BCR-ABL1 fusion gene was positive. Genetic testing at the time of recurrence revealed presence of a heterozyous c.944C>T variant in the kinase region of the ABL1 gene. FISH showed a signal for ABL1-BCR fusion on both chromosome 9s. CMA showed that the mosaicism homozygosity ratio of chromosome 9 was about 40%, and the mosaicism duplication ratio of chromosome 22 was about 43%. CONCLUSION Since both der(9) homologs were seen in 40% of cells, the possible mechanism for the double der(9) in this patient may be similar to that of double Ph, which might have resulted from non-disjunction during mitosis in the Ph chromosome-positive cell clone.
Humans ; Philadelphia Chromosome ; In Situ Hybridization, Fluorescence/methods* ; China ; Chromosome Aberrations ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Translocation, Genetic ; Fusion Proteins, bcr-abl/genetics* ; Chromosomes, Human, Pair 9/genetics*

A variant Philadelphia chromosome (Ph) is generated from translocation of one or more partner chromosomes in addition to chromosomes 9 and 22. We have described the cases of 2 patients bearing variant Ph detected by interphase FISH but not detected by G-banded karyotyping and metaphase FISH. FISH was performed using BCR/ABL dual color dual fusion translocation probes (Abbott Molecular, USA). A 52-year-old man was diagnosed with acute leukemia of mixed phenotype. G-banded karyotyping showed 46,XY,t(9;22)(q34;q11.2)[12]/47,idem,+der(22)t(9;22)[5]/46,XY[3]. Interphase FISH revealed nuc ish(ABL1,BCR)x3(ABL1 con BCRx2)[329/450]/(ABL1,BCR)x4(ABL1 con BCRx3)[5/450]/(AL1,BCR)x3(ABL1 con BCRx1)[44/450]. Metaphase FISH showed ish (9;22)(ABL1+,BCR1+;BCR+,ABL+)[22]/der(22)(BCR+,ABL1+)[3]. The other case was that of a 31-yr-old male patient diagnosed with CML in the blastic phase. G-banded karyotyping of all 20 metaphase cells showed 47,XYYc,dup(1)(q21q32),del(7)(p11.2),t(9;22)(q34;q11.2). Interphase FISH revealed nuc ish(ABL1,BCR)x3(ABL1 con BCRx2)[254/600]/(ABL1,BCR)x3(ABL1 con BCRx1)[191/600]. Metaphase FISH showed ish t(9;22)(ABL1+,BCR+;BCR+,ABL1+)[16]. These results suggest that typical t(9;22) and variant Ph may coexist in the same patient, and interphase FISH may facilitate the detection of the variant Ph that cannot be detected by G-banded karyotyping alone.
Adult ; Chromosomes, Human, Pair 22 ; Chromosomes, Human, Pair 9 ; Humans ; In Situ Hybridization, Fluorescence/*methods ; Interphase ; Karyotyping ; Leukemia/diagnosis/genetics ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis/genetics ; Male ; Metaphase ; Middle Aged ; Phenotype ; *Philadelphia Chromosome ; Translocation, Genetic

OBJECTIVETo determine the frequency of the derivative 9 [der(9)] deletion among chronic myeloid leukemia (CML) patients with classic and variant Ph translocations, and assess the correlation between this deletion and clinical prognosis.

METHODSCytogenetic analysis of bone marrow cells was performed by direct method and/or 24 h culture method. RHG banding was used for karyotype analysis. Dual-color and dual-fusion DNA probe was used to perform FISH for investigating the deletion of der(9) in Ph+ CML patients.

RESULTSCytogenetics studies showed typical Ph translocation in 76/105 and variant Ph translocation in 29/105 cases. Interphase-FISH studies showed deletion of der(9) in 12 (15.8%) of 76 patients with classic Ph translocation and in 4 (13.7%) of 29 patients with variant translocation. The frequency of deletion was similar in classic and variant translocations (P > 0.05). When the deletion was seen in the patient, it was present in all the Ph+ metaphases and nuclei. In 3 patients there were mixed cell populations with either 5'-abl or 3'-bcr deletion and all the 3 patients had both 5'-abl and 3'-bcr deletion. The median survival time of patients with deletion was significantly shorter than those without deletion (34 months vs 76 months; P < 0.05).

CONCLUSIONDeletion of der(9) is seen in about 1/6 of Ph+ CML patients in our study on Chinese CML patients, Ph+ CML patients with the deletion have shorter median survival time than those without it, indicating that it is a poor prognostic index.

Adolescent ; Adult ; Aged ; Child ; Chromosome Deletion ; Chromosomes, Human, Pair 9 ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; diagnosis ; genetics ; mortality ; Male ; Middle Aged ; Philadelphia Chromosome ; Prognosis ; Survival Rate ; Translocation, Genetic ; Young Adult

Chromosome Aberrations ; Chromosomes, Human, Pair 16 ; Chromosomes, Human, Pair 9 ; Humans ; Infant, Newborn ; Male

BACKGROUND: The complementary ABL-BCR gene rearrangement is formed at chromosome 9 parallel to the Ph chromosome at der(22)t(9;22), which has been found deleted in a minority of chronic myelogenous leukemia (CML) patients. This study was designed to analyze the deletion status of ABL and/or BCR on derivative chromosome 9 and to evaluate the prognostic significance of the deletion of these genes in CML. METHODS: We studied 79 patients who were diagnosed as CML at Seoul National University Hospital between January 1997 and February 2002. The deletion status of ABL and BCR on derivative chromosome 9 was investigated by interphase fluorescent in situ hybridization (FISH) method. RESULTS: ABL deletion was detected in 14 (17.7%) patients and BCR deletion was observed in 8 patients (10.1%). Event-free survival time of the patients with ABL and/or BCR deletion (19.0%) was shorter than that of the patients without any deletion of these two genes (median, 40.0 months vs. 92.0 months)(P=0.027). Twenty seven patients progressed to blast crisis in this period. The period to blast crisis was also shorter in 8 patients with ABL and/or BCR deletion than in 19 patients without any gene deletion (P=0.044). The b2a2 mRNA type was more frequent in the patients with ABL deletion only than in the patients without any gene deletion (P=0.034). CONCLUSIONS: Event-free survival time and the period to blast crisis were significantly shorter in patients with deletion of ABL and/or BCR on derivative chromosome 9. ABL and/or BCR deletion can be a significant prognostic marker that indicates rapid disease progression.
Blast Crisis ; Chromosomes, Human, Pair 9* ; Disease Progression ; Disease-Free Survival ; Gene Deletion ; Gene Rearrangement ; Humans ; Hydrogen-Ion Concentration ; In Situ Hybridization, Fluorescence ; Interphase ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive* ; Philadelphia Chromosome ; RNA, Messenger ; Seoul

Atherosclerosis ; genetics ; Chromosomes, Human, Pair 9 ; Humans ; RNA, Long Noncoding

Split hand split foot malformation (SHFM) is a human developmental disorder characterized by a deep median cleft in the hands and feet, missing digits, and fusion of the remaining digits. The disease itself is considered to be very rare, affecting one out of 90,000 newborn babies. SHFM is genetically heterogeneous. To date, five SHFM loci have been mapped, to chromosome 2, 3, 7, 10 and X, respectively. We experienced a case of SHFM in a male neonate who had lobster-claw deformities of the hands and feet. The karyotype of his chromosome was 46,XY,inv (9) (p12q13). We report the case with the review of the associated literatures.
Chromosomes, Human, Pair 2 ; Chromosomes, Human, Pair 9* ; Congenital Abnormalities ; Foot* ; Hand* ; Human Development ; Humans ; Infant, Newborn ; Karyotype ; Male

A phenotypically normal couple was referred for cytogenetic evaluation due to three consecutive first-trimester spontaneous abortions. Chromosomal analysis from peripheral blood was performed according to standard cytogenetic methods using G-banding technique. The husband's karyotype was normal. The wife's karyotype showed a balanced complex chromosome rearrangement (CCR) involving chromosomes 9,14, and 13. There were three breakpoints: 9p21.2, 14q21, and 13q12.2. The karyotype was designated as 46, XX, t (9;14;13)(p21.2;q21; q12.2). Fluorescence in situ hybridization (FISH) analysis with chromosome-specific libraries of chromosomes 9,14, and 13 was performed to confirm this rare chromosome rearrangement. The result of FISH coincided with that obtained by standard cytogenetic techniques.
Abortion, Habitual/*genetics ; Adult ; Case Report ; *Chromosome Aberrations ; *Chromosomes, Human, Pair 13 ; *Chromosomes, Human, Pair 14 ; *Chromosomes, Human, Pair 9 ; Female ; Human ; In Situ Hybridization, Fluorescence ; Pregnancy

OBJECTIVETo explore the genetic and clinical characteristics of isodicentric Ph chromosomes [idic(Ph)] in lymphoid blast crisis of chronic myeloid leukemia (CML-BLC).

METHODSBone marrow aspirates of 2 patients with CML-BLC were analyzed by R banding after 24 hours of culturing. Genomic copy number variations (CNV) were analyzed by single nucleotide polymorphism array (SNP array) in case 1. The results were confirmed with fluorescence in situ hybridization (FISH). Variations of acute lymphoblastic leukemia-related genes including CDKN2A/AB and PAX5 were detected by multiplex ligation-dependent probe amplication (MLPA).

RESULTSDeletions and duplications on derivative chromosome 9 detected by FISH were confirmed by SNP array analysis. The distances between the BCR/ABL fusion signals on the idic(Ph) chromosomes in the two patients have differed greatly. The idic(Ph) in the second patient was supposed to be formed by two Ph chromosomes joined at their q terminals, where as the idic(Ph) in the first patient have been shown to be fused at the satellite regions of their p arms.

CONCLUSIONThe idic(Ph) chromosomes presented in CML-BLC may predict resistance to Imatinib and response to Dasatinib.

Blast Crisis ; diagnosis ; genetics ; therapy ; Chromosome Aberrations ; Chromosome Banding ; Chromosome Deletion ; Chromosome Duplication ; Chromosomes, Human, Pair 9 ; genetics ; DNA Copy Number Variations ; Fatal Outcome ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; diagnosis ; genetics ; therapy ; Male ; Middle Aged ; Philadelphia Chromosome