Clinical presentation and natural history of patients with essential thrombocythemia and the Philadelphia chromosome

Stoll, Dominik; Peterson, Powers; Exten, Robert E.; László, John; Pisciotta, Anthony V.; Ellis, John Tracy; White, Patrick B.; Vaidya, Kalpana; Bozdech, Marek J.; Murphy, Scott

doi:10.1002/ajh.2830270202

Cited by 76 publications

(37 citation statements)

References 21 publications

(6 reference statements)

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“…Yet only after progression to accelerated phase were chromosome studies performed which established the diagnoses of CML. The PVSG mandate for karyotyping was stimulated by their experience with six young women who were Philadelphia chromosome positive but otherwise fulfilled diagnostic criteria for ET [7]. These six women all had features that suggested the possibility of CML from the outset, including leukocytosis, leukoerythroblastosis, and/or basophilia.…”

Section: Discussionmentioning

confidence: 99%

Every case of essential thrombocythemia should be tested for the Philadelphia chromosome

Rice

Popat

2004

Am. J. Hematol.

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Essential thrombocythemia (ET) and chronic myelogenous leukemia (CML) usually present with distinctive features. Citing experience with cases that overlap, the Polycythemia Vera Study Group recommends that negative tests for the Philadelphia chromosome be obtained before diagnosing ET. We describe two young women presenting with features absolutely typical for ET, including extreme thrombocytosis, no leukocytosis, no basophilia, no peripheral immature cells, and no splenomegaly. Severe thrombotic complications ensued: multiple cerebrovascular thromboemboli, pulmonary emboli, and miscarriage in one and myocardial infarction in the other. By 4 years, both developed leukocytosis, extreme basophilia, and circulating blasts, typical of accelerated CML. Cytogenetic studies were then performed, revealing the Philadelphia chromosome. Imatinib produced rapid clearing of blasts and basophils, but one woman later succumbed after allogeneic bone marrow transplant and the other has not achieved a major cytogenetic response. We conclude that CML can present in identical fashion as ET. The mandate for routine Philadelphia chromosome testing is magnified by the availability of targeted therapy and its greater efficacy in early stage disease. Am.

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Section: Discussionmentioning

confidence: 99%

Every case of essential thrombocythemia should be tested for the Philadelphia chromosome

Rice

Popat

2004

Am. J. Hematol.

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“…15 However, our case differs in that the transcript was similar to the b2a2 transcript with an inserted sequence, the disease resembling ET due to the marked thrombocytosis, absence of splenomegaly, and normal LAP score. Early reports of ET with a Ph chromosome 1 have not included detailed molecular genetic studies but have indicated that the prognosis in ET was similar to that in CML. A later study 13 noted that the BCR/ABL transcript was not detected in four ET cases who were Ph chromosome negative.…”

Section: Discussionmentioning

confidence: 99%

“…Opinions have differed whether the absence of the Philadelphia chromosome (Ph) is required for ET diagnosis. Some [1][2][3] have studied Ph + ET whereas others discuss CML with thrombocythemic onset. 4,5 CML is characterized by leukaemic cells bearing the Philadelphia chromosome, a t(9;22)(q34;q11) reciprocal translocation that results in a BCR/ABL fusion gene and a 210 kDa protein product involving the BCR gene of chromosome 22 and the ABL gene of chromosome 9.…”

Section: Introductionmentioning

confidence: 99%

A novel BCR-ABL rearrangement in a Philadelphia chromosome-positive chronic myelogenous leukaemia variant with thrombocythaemia

Rubinstein

1998

Leukemia

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Reverse transcription polymerase chain reaction was used to detect an unusual BCR/ABL transcript in a patient who presented with thrombocythaemia and was Philadelphia chromosome positive but weakly reactive to conventional BCR/ABL fusion probes. Sequencing revealed the presence of a 12 bp insert between BCR exon2 (b2) and ABL exon2 (a2). In such cases the use of conventional BCR/ABL probes may lead to false negative results. This is the first report of this transcript. Clinically the patient has responded well to therapy.

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“…Our results confirm the presence of BCR-ABL positivity by PCR in some patients with ET, albeit at a lower frequency than that reported by Blickstein et al We analyzed peripheral blood samples, but higher frequencies have been reported in bone marrow. Although the presence of the Ph chromosome in ET carries a poor prognosis, 8 the clinical significance of BCR-ABL positivity in Ph-negative ET at various levels of sensitivity remains unclear. The finding of this molecular abnormality by PCR in our patients doesn't seem to imply a diagnosis of CML, as suggested by the absence of clinical features of CML, their long-term uneventful follow-up, and the spontaneous disappearance of BCR-ABL transcripts in one of them.…”

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confidence: 99%

BCR-ABL transcripts may be detected in essential thrombocythemia but lack clinical significance

Heller¹,

Kornblihtt²,

Cuello³

et al. 2001

Blood

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We read with interest the letter of Emilia et al 1 concerning the absence of BCR-ABL rearrangement in essential thrombocythemia (ET). They studied 112 patients with ET with nested reverse transcriptase-polymerase chain reaction (RT-PCR) and found only one BCR-ABL ϩ patient who progressed to myelofibrosis and blast crisis 12 years after diagnosis. Based on their findings, the authors conclude that the presence of BCR-ABL rearrangement in ET identifies a subset of patients at risk for progression to acute leukemia and suggest that these patients probably represent chronic myelogenous leukemia (CML) of thrombocythemic onset. We do not share their opinion on the basis of our own experience.We used single and nested RT-PCR and interphase fluorescence in situ hybridization (FISH) to prospectively evaluate 47 patients with ET who fulfilled the criteria of the Polycythemia Vera Study Group (32 women; median age 49 years, range 14-80 years). Ten patients were untreated, 31 were treated with anagrelide, and 6 were treated with hydroxyurea. Median platelet count was 1300 ϫ 10 9 /L (range 608-3742 ϫ 10 9 /L), 20 patients had mild leukocytosis, none had basophilia, 3 had a borderline low leukocyte alkaline phosphatase (LAP) score. Twenty patients had mild splenomegaly and 15 had focal reticulin fibrosis. None of the 40 cytogenetic studies performed revealed the Ph chromosome.One-step and nested RT-PCR for BCR-ABL transcripts (b3a2 and b2a2 subtypes) were performed on peripheral blood samples using methodology described by Kawasaki et al 2 and Cross et al, 3 respectively, with slight modifications, with a sensitivity of 10 Ϫ4 and 10 Ϫ6 determined by K562 cell dilution. Assays were carried out with appropriate controls and 20 healthy individuals were BCR-ABL Ϫ . FISH analysis was performed on peripheral blood smears as described. 4 In 5000 bone marrow cells from 25 controls the BCR-ABL extra signal (ES) probe (Vysis, Downers Grove, IL) demonstrated 1 yellow (fusion) signal, 1 green signal, and 2 red signals (BCR-ABL fusion positive pattern) in 0.14% (0.3% [3 SD ϭ 0.9%]), with a sensitivity of 98.5%. For each patient, 200 nuclei were scored.Three Ph chromosome-negative patients were found to harbor b3a2 BCR-ABL fusion transcripts by RT-PCR (6.4 %). Both one-step and nested PCR results were positive in 1 patient; only nested PCR yielded positive results in the other 2 patients. BCR-ABL transcripts were detected in the first patient at diagnosis and several times during follow-up while on treatment with anagrelide. The other 2 BCR-ABL ϩ patients were first evaluated during treatment with anagrelide. Repeated samples remained positive in the second patient while negative PCR results were obtained on sequential analysis in the third patient. Interphase FISH results on these patients showed lack of fusion signal. Follow-up was 73, 68, and 116 months, respectively. Clinical and laboratory features in patients with positive results did not differ from the BCR-ABL Ϫ group and they followed an uneventful course. Median follow-up in the ...

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Clinical presentation and natural history of patients with essential thrombocythemia and the Philadelphia chromosome

Cited by 76 publications

References 21 publications

Every case of essential thrombocythemia should be tested for the Philadelphia chromosome

Every case of essential thrombocythemia should be tested for the Philadelphia chromosome

A novel BCR-ABL rearrangement in a Philadelphia chromosome-positive chronic myelogenous leukaemia variant with thrombocythaemia

BCR-ABL transcripts may be detected in essential thrombocythemia but lack clinical significance

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