# Chronic Myeloid Leukaemia with isolated massive thrombocytosis and BCR-ABL1 detection failure using RT-MLPA (positive RT-qPCR)

Lucie Coster, Véronique Mansat-de Mas, Laetitia Largeaud, Sophie Voisin, Jill Corre, Martin Gauthier

► To cite this version:

Lucie Coster, Véronique Mansat-de Mas, Laetitia Largeaud, Sophie Voisin, Jill Corre, et al.. Chronic Myeloid Leukaemia with isolated massive thrombocytosis and BCR-ABL1 detection failure using RT-MLPA (positive RT-qPCR). eJHaem, 2021, 2 (3), pp.655-656. 10.1002/jha2.207. hal-05043948

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Submitted on 23 Apr 2025

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# Chronic Myeloid Leukaemia with isolated massive thrombocytosis and BCR-ABL1 detection failure using RT-MLPA (positive RT-qPCR)

Lucie Coster<fnref n="1" />

<figure><img src="image_2.png" /></figure>

Véronique Mansat-De MAS<fnref n="1" />,<fnref n="2" />

<figure><img src="image_3.png" /></figure>

Laetitia Largeaud<fnref n="1" />,<fnref n="2" />

<figure><img src="image_4.png" /></figure>

Sophie Voisin<fnref n="1" />

<figure><img src="image_5.png" /></figure>

Jill Corre<fnref n="1" />,<fnref n="2" />

<figure><img src="image_6.png" /></figure>

Martin Gauthier<fnref n="3" />

<figure><img src="image_7.png" /></figure>

**Correspondence**

Lucie Coster, Department of Haematology-Biology, centre hospitalier universitaire de Toulouse, IUCT-O, 1 avenue Irène Joliot-Curie, 31059 Toulouse Cedex 9, France.

Email: coster.lucie@iuct-oncopole.fr

**KEYWORDS**

CML, CML BCR-ABL, haemostasis, leukaemia cytogenetics, molecular analysis, PCR

A 48-year-old woman with no medical history was referred for incidental discovery of thrombocytosis. The full blood count showed discrete anaemia and severe thrombocytosis (haemoglobin concentration 116 g/L, platelets 805 × 10⁹/L), with no increase of any leukocyte (neutrophils 5.1 × 10⁹/L, basophils 0.1 × 10⁹/L) or immature granulocytes. The initial etiological investigation revealed no cause of reactive thrombocytosis, nor JAK2, CALR or MPL mutation (blood samples). Moreover, RT-MLPA (reverse transcription multiplex ligation-dependent probe amplification) was considered negative for BCR-ABL1 in blood sample, because in background noise. While awaiting the results of those investigations, she rapidly developed massive thrombocytosis, with no response to hydroxycarbamide and spontaneous oral cavity bleeding despite no previous bleeding. Low von Willebrand activity (0.08 IU/ml) confirmed an acquired von Willebrand syndrome (AVWS), with decreased factor VIII (0.65), and discordance between von Willebrand activity and von Willebrand antigen (0.60), excluding a trephine biopsy. Concomitantly, platelet count reached 3.699 × 10⁹/L and basophil count reached 0.7 × 10⁹/L (6% of leukocytes), while other haematologic parameters remained within normal range.

Bone marrow smear examination (May-Grünwald-Giemsa) showed hypolobated megakaryocytes (10x objective, red arrow), and 3% of basophils (100x objective, red arrow). Bone marrow karyotype found a t(9;22;17)(q34;q11;p13) translocation, a variant translocation of the classic t(9;22) with a partner chromosome 17, not considered as

an additional chromosomal abnormality (ACA), within only 9 over 20 mitoses (with neither i(17)(q10) nor TP53 deletion) and a low FISH positivity (24% nuclei with BCR-ABL1 fusion) (yellow arrows). A diagnosis of chronic myeloid leukaemia (CML) was established and the patient was treated with nilotinib, allowing rapid platelet count normalization (1 month) and subsequent AWVS disappearance (von Willebrand activity, 0.72 and antigen, 0.87). The patient presented a rapid decrease in BCR-ABL1 transcript and reached both complete cytogenetic and deep molecular response within 3 months (transcript 0.0005%, International scale [IS]), with an undetectable transcript thereafter.

CML presenting with isolated extreme thrombocytosis is a rare but well-known entity affecting younger patients and more often women. RT-MLPA failed to detect BCR-ABL1 and our patient had the lowest BCR-ABL1 transcript at CML diagnosis in our laboratory (3.6% [IS] RT-qPCR, comparison with 123 patients) (red square); the BCR-ABL1 transcript observed was typical e13a2 responsible for the presence of a p210 BCR-ABL1 protein. This point could raise issues about BCR-ABL1 transcript value at diagnosis of CML patients presenting with isolated thrombocytosis. Anyway, our case points that, RT-MLPA, performed on blood sample in isolated thrombocytosis CML suspicion may be questionable and should systematically be checked using RT-qPCR, which has a better sensitivity. Additionally, we illustrate that, in the case of isolated thrombocytosis, AVWS is frequent, and the presence of hypolobated megakaryocytes and basophils may lead to CML

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

© 2021 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.

<footnote n="1">¹ Service d'Hématologie biologique, Centre Hospitalier Universitaire de Toulouse, IUCT-O, Toulouse, France</footnote>

<footnote n="2">² Université Paul Sabatier Toulouse III, Toulouse, France</footnote>

<footnote n="3">³ Service d'Hématologie clinique, Centre Hospitalier Universitaire de Toulouse, IUCT-O, Toulouse, France</footnote>
diagnosis and not to essential thrombocythemia as megakaryocytes
are big and hyperlobed with no basophils in this latter case.

## DISCLOSURE OF CONFLICTS OF INTEREST

The authors declare they have no conflict of interest.

## CONFLICT OF INTEREST

The authors declare no conflict of interest.

## ETHICS APPROVAL

This article does not contain any studies with human participants per-
formed by any of the authors.

## PATIENT CONSENT

Informed consent was not required in this study.

## DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the
corresponding author upon reasonable request.

## AUTHOR CONTRIBUTIONS

Lucie Coster performed cytogenetic analyses; Véronique Mansat-
De Mas and Laetitia Largeaud performed RT-MLPA and RT-qPCR

analyses; Sophie Voisin performed haemostasis analyses; Véronique
Mansat-De Mas and Jill Corre performed bone marrow smear exami-
nation; Martin Gauthier managed the patient; Martin Gauthier, Lucie
Coster and Véronique Mansat-De Mas wrote the manuscript. All
authors revised and approved the manuscript.

## ORCID

Lucie Coster https://orcid.org/0000-0001-7993-7485

Véronique Mansat-De MAS https://orcid.org/0000-0003-1878-9129

Laetitia Largeaud https://orcid.org/0000-0001-5341-5427

Sophie Voisin https://orcid.org/0000-0002-2871-166X

Jill Corre https://orcid.org/0000-0003-1580-6106

Martin Gauthier https://orcid.org/0000-0001-5338-2071

**How to cite this article:** Coster L, Mansat-De MAS V, Largeaud L, Voisin S, Corre J, Gauthier M. Chronic Myeloid Leukaemia with isolated massive thrombocytosis and BCR-ABL1 detection failure using RT-MLPA (positive RT-qPCR). eJHaem. 2021;2:655-656. https://doi.org/10.1002/jha2.207