Acute myelomonocytic leukemia with inv(16)(p13q22) complicating Philadelphia chromosome positive chronic myeloid leukemia

Heim, Sverre; Christensen, Bjarne; Fioretos, Thoas; Sørensen, Anne G.; Pedersen, Niels Tinggaard

doi:10.1016/0165-4608(92)90154-z

Cited by 39 publications

(11 citation statements)

References 23 publications

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“…Therefore, a clear distinction of de novo AML and CML blast crisis remains challenging even in these inv(16)+ cases. The distribution of BCR-ABL p190 and p210 in inv(16)-CBF-AML was notably different from CML blast crisis: 53 % (9 cases) carried the p190 transcript in AML, whereas p190 was only found in one of 19 published cases of CML-AP/BC with inv (16) [18,19,[39][40][41][42][43][44][45][46][47][48]. Therefore, the detection of the minor BCR-ABL transcript in AML with inv(16) might be helpful in identifying de novo BCR-ABL+ AML.…”

Section: Characteristic Features Of Bcr-abl+ Amlmentioning

confidence: 99%

BCR-ABL-positive acute myeloid leukemia: a new entity? Analysis of clinical and molecular features

et al. 2016

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BCR-ABL-positive acute myeloid leukemia (AML) is a rare subtype of AML that is now included as a provisional entity in the 2016 revised WHO classification of myeloid malignancies. Since a clear distinction between de novo BCR-ABL+ AML and chronic myeloid leukemia (CML) blast crisis is challenging in many cases, the existence of de novo BCR-ABL+ AML has been a matter of debate for a long time. However, there is increasing evidence suggesting that BCR-ABL+ AML is in fact a distinct subgroup of AML. In this study, we analyzed all published cases since 1975 as well as cases from our institution in order to present common clinical and molecular features of this rare disease. Our analysis shows that BCR-ABL predominantly occurs in AML-NOS, CBF leukemia, and AML with myelodysplasia-related changes. The most common BCR-ABL transcripts (p190 and p210) are nearly equally distributed. Based on the analysis of published data, we provide a clinical algorithm for the initial differential diagnosis of BCR-ABL+ AML. The prognosis of BCR-ABL+ AML seems to depend on the cytogenetic and/or molecular background rather than on BCR-ABL itself. A therapy with tyrosine kinase inhibitors (TKIs) such as imatinib, dasatinib, or nilotinib is reasonable, but-due to a lack of systematic clinical data-their use cannot be routinely recommended in first-line therapy. Beyond first-line treatment of AML, the use of TKI remains an individual decision, both in combination with intensive chemotherapy and/or as a bridge to allogeneic stem cell transplantation. In each single case, potential benefits have to be weighed against potential risks.

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Section: Characteristic Features Of Bcr-abl+ Amlmentioning

confidence: 99%

BCR-ABL-positive acute myeloid leukemia: a new entity? Analysis of clinical and molecular features

et al. 2016

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“…Already in 1983, Berger et al [86]described the presence of t(15;17)(q22;q12–21), almost pathognomonic for acute promyelocytic leukemia, in addition to t(9;22) in a case of CML with promyelocytic BC, and since then, close to 10 such cases have been reported [47]. Other balanced rearrangements characteristically found in acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) but occasionally also in CML BC include inv(3)(q21q26)/t(3;3)(q21;q26), t(3;21) (q26;q22), t(7;11)(p15;p15), t(8;21)(q22;q22), and inv(16) (p13q22) [47, 87, 88, 89, 90, 91]. Although secondary by definition, these additional changes do not behave as ordinary secondary changes.…”

Section: Cytogenetic Evolution In the Banding Eramentioning

confidence: 99%

Cytogenetic and Molecular Genetic Evolution of Chronic Myeloid Leukemia

2002

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Chronic myeloid leukemia (CML) is genetically characterized by the presence of the reciprocal translocation t(9;22)(q34;q11), resulting in a BCR/ABL gene fusion on the derivative chromosome 22 called the Philadelphia (Ph) chromosome. In 2–10% of the cases, this chimeric gene is generated by variant rearrangements, involving 9q34, 22q11, and one or several other genomic regions. All chromosomes have been described as participating in these variants, but there is a marked breakpoint clustering to chromosome bands 1p36, 3p21, 5q13, 6p21, 9q22, 11q13, 12p13, 17p13, 17q21, 17q25, 19q13, 21q22, 22q12, and 22q13. Despite their genetically complex nature, available data indicate that variant rearrangements do not confer any specific phenotypic or prognostic impact as compared to CML with a standard Ph chromosome. In most instances, the t(9;22), or a variant thereof, is the sole chromosomal anomaly during the chronic phase (CP) of the disease, whereas additional genetic changes are demonstrable in 60–80% of cases in blast crisis (BC). The secondary chromosomal aberrations are clearly nonrandom, with the most common chromosomal abnormalities being +8 (34% of cases with additional changes), +Ph (30%), i(17q) (20%), +19 (13%), –Y (8% of males), +21 (7%), +17 (5%), and monosomy 7 (5%). We suggest that all these aberrations, occurring in >5% of CML with secondary changes, should be denoted major route abnormalities. Chromosome segments often involved in structural rearrangements include 1q, 3q21, 3q26, 7p, 9p, 11q23, 12p13, 13q11–14, 17p11, 17q10, 21q22, and 22q10. No clear-cut differences as regards type and prevalence of additional aberrations seem to exist between CML with standard t(9;22) and CML with variants, except for slightly lower frequencies of the most common changes in the latter group. The temporal order of the secondary changes varies, but the preferred pathway appears to start with i(17q), followed by +8 and +Ph, and then +19. Molecular genetic abnormalities preceding, or occurring during, BC include overexpression of the BCR/ABL transcript, upregulation of the EVI1 gene, increased telomerase activity, and mutations of the tumor suppressor genes RB1, TP53, and CDKN2A. The cytogenetic evolution patterns vary significantly in relation to treatment given during CP. For example, +8 is more common after busulfan than hydroxyurea therapy, and the secondary changes seen after interferon-alpha treatment or bone marrow transplantation are often unusual, seemingly random, and occasionally transient. Apart from the strong phenotypic impact of addition of acute myeloid leukemia/myelodysplasia-associated translocations and inversions, such as inv(3)(q21q26), t(3;21)(q26;q22), and t(15;17)(q22;q12–21), in CML BC, only a few significant differences between myeloid and lymphoid BC are discerned, with i(17q) and TP53 mutations being more common in myeloid BC and monosomy 7, hypodiploidy, and CDKN2A deletions being more frequent in lymphoid BC. The prognostic significance of the secondary genetic changes is not uniform, althoug...

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“…1,5 Several patients with AML type 4 in conjunction with GS and abnormalities of chromosome 16, mainly inv(16)(p13;q22) have also been reported. 3,[6][7][8] However, isolated granulocytic sarcoma of the small intestine preceding AML is rare; only two patients had a cytogenetic analysis using banding techniques. Le Beau et al Our patient has several features in common with the latter case (inv(16) and double trisomies 9 and 22), but for the absence of eosinophilia and the type of AML which is definitely of the FAB type 2; however, the blasts composing the granulocytic sarcoma had some monocytic characteristics which were not found in the marrow at the diagnosis of the AML.…”

Section: Figurementioning

confidence: 99%

Isolated granulocytic sarcoma followed by acute myelogenous leukemia type FAB-M2 associated with inversion 16 and trisomies 9 and 22

et al. 2002

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Isolated granulocytic sarcoma followed by acute myelogenous leukemia type FAB-M2 associated with inversion 16 and trisomies 9 and 22 Leukemia (2002) 16, 2458-2459. doi:10.1038/sj.leu.2402593 TO THE EDITOR Granulocytic sarcoma (GS), also known as chloroma, are extramedullary tumors composed of immature myeloid cells. They have been described in a wide variety of anatomical sites, including breast, ovary, brain, gastrointestinal tract and skull.1,2 They occur at the onset of acute myelogenous leukemia (AML) or during its evolution. They may also be the first sign of acute transformation of myelodysplastic syndromes and chronic myeloproliferative disorders. They are rarely the first manifestation of AML. GS are observed in only 2 to 8% of AML, mainly of M2 morphology, although they have also been associated with M3, M4, M5, and M7 morphology.A 37-year-old man was referred to our hospital in June 1999. He had a history of ascitis and intestinal occlusion due to three stenotic lesions of the jejunum. A large peritoneal mass was noted. The patient had surgery in March 1999 during which a partial resection of the proximal jejunum was performed. The histologic examination of the surgical piece was interpreted as a massive lymphomatous infiltration of the whole intestine wall. In May 1999, he had surgery again because of necrosis of the tumor with cutaneous fistula. A bone marrow biopsy and a complete blood count were normal. The patient received two courses of anti-lymphoma chemotherapy.Because of the lack of response, he was admitted to the hematology service. The patient had ileus, ascitis, severe deterioration of his health status and a 13 kg weight loss. A blood count showed a hemoglobin of 10.5 g/dl, a white blood cell (WBC) count of 4.4 × 10 9 /l and a platelet count of 343 × 10 9 /l. The leukocyte differential showed 84% neutrophils, 15% lymphocytes and 1% monocytes.A review of the original histology found the malignant cells to be blasts. These cells were shown to contain myeloperoxidase and to express CD34 and CD68 antigens. Furthermore, immunophenotyping was partially positive for CD15 and lysozyme. A retrospective diagnosis of isolated granulocytic sarcoma was made. Unfortunately, no material was available for cytogenetic studies.The bone marrow aspirate and the blood cell count were still normal. At the end of July 1999, chemotherapy with aracytidine and idarubicin was started, leading to the disappearance of all abdominal signs and a complete remission. No complementary radiotherapy was performed because of the small bowel localization of the granulocytic sarcoma. Then, the patient received a consolidation therapy with high Hematopoietic reconstruction was incomplete, without any signs of acute leukemia. The patient was hospitalized again at the end of August 2000 because of the presence of 39% circulating blasts. A bone marrow aspirate showed hypercellularity with 72% myeloblasts, some containing Auer rods and showing discrete abnormal granular maturation, leading to the diagnosis of AML type 2. The bl...

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Acute myelomonocytic leukemia with inv(16)(p13q22) complicating Philadelphia chromosome positive chronic myeloid leukemia

Cited by 39 publications

References 23 publications

BCR-ABL-positive acute myeloid leukemia: a new entity? Analysis of clinical and molecular features

BCR-ABL-positive acute myeloid leukemia: a new entity? Analysis of clinical and molecular features

Cytogenetic and Molecular Genetic Evolution of Chronic Myeloid Leukemia

Isolated granulocytic sarcoma followed by acute myelogenous leukemia type FAB-M2 associated with inversion 16 and trisomies 9 and 22

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