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Philadelphia chromosome positive chronic myeloid leukemia with 5q deletion at diagnosis



Although, molecular genetic analyses became more and more important to guide therapy decisions in leukemia, banding cytogenetic analysis has retained its vital role in diagnosis and monitoring of chronic myeloid leukemia (CML), by quick and easy enabling identification of pathognomonic Philadelphia chromosome (Ph).

Case presentation

A 45 year old female presented with characteristic hematological features of CML in chronic phase; cytogenetic studies revealed the presence of the typical Ph and a deletion of almost entire long arm of a chromosome 5.


5q deletions have rarely been reported in CML. Those seen yet were either associated with tyrosine kinase inhibitor therapy or detected post allogeneic stem cell transplantation. To our knowledge, this is the first case of Ph positive CML accompanied by a 5q deletion.


Chronic myelogenous leukemia (CML), results from a balanced translocation t(9;22)(q34;q11.2) giving rise to the BCR-ABL1 chimeric gene being the oncogenic driver of CML [1]. This fusion gene is not only pathognomonic diagnostic marker of but also therapeutic target for CML [2]. Since the introduction of Imatinib as the first medication with tyrosine kinase inhibitor (TKI) activity there was continuous advancement in CML management, not only by refinement of diagnostic and monitoring modalities but also by introduction of multiple generations of TKI agents, leading to better disease outcomes [3, 4]. Besides cytogenetics, molecular cytogenetics is an essential pillar for the diagnosis and monitoring of patients with CML [5]. Quantitative polymerase chain reaction (Q-PCR) to detect low levels of BCR-ABL1 fusion gene presence has now enabled for deeper scrutiny into the disease, allowing to identify abnormal clones as small as 1 in 10,000 cells [6, 7]. Accordingly, patients achieving and maintaining deep molecular response (i.e. having a negative Q-PCR-test result) are entitled for complete discontinuation of TKI therapy [8]. Although, the mentioned molecular achievements in diagnosis and monitoring of CML have been essential for progress in disease management, the role of cytogenetic studies is undeniably still significant, as those allow for identification of additional chromosome abnormalities of prognostic significance [9]. This is as additional cytogenetic abnormalities may be acquired during course of disease and/or therapy, i.e. clonal evolution may take place [10, 11]. Such additional cytogenetic abnormalities may have significant effect on the disease profile and response to therapy [12].One of the rarely seen additional cytogenetic abnormalities is deletion in the long arm of a chromosome 5 (5q-); however, this has been reported yet only in CML-patients under during therapy [13, 14].

Here we present a case with classic clinical and hematological features of CML in chronic phase where banding cytogenetics revealed presence of a Philadelphia chromosome (Ph) along with deletion del(5)(q13.3).

Case presentation

A 45-year old female, without any significant past medical illness, presented with lethargy, anorexia and pallor, which progressively developed over 6 months. On examination, the patient was mildly pale, and abdominal examination revealed moderately enlarged spleen without hepatomegaly. Complete blood count (CBC) revealed moderate anemia, hyperleukocytosis (130 × 103 white blood cells per microliter), demonstrating predominance of granulopoesis with bimodal peak of mature neutrophils (51%) and myelocytes (29%). The blast count was less than 1% and there was no basophilia. With an initial suspected diagnosis of CML cytogenetic analysis was performed. Peripheral blood was sampled for conventional non-phytohemagglutinine-stimulated karyotyping. All 20 analyzed metaphases revealed a karyotype 46,XX,del(5)(q13.3),t(9;22)(q34;q11.2) (Fig. 1). After confirming suspicion of CML by this, TKI therapy was initiated, under which the patient does well up to now.

Fig. 1
figure 1

A typical metaphases of the reported patient showing a karyotype of 46,XX,del(5)(q13.3),t(9;22)(q34;q11.2)


CML, once an indefinitely progressive hematological malignancy, is now a success story in the field of hemato-oncology [15]. Patients, when treated properly, now achieve complete molecular remission within weeks to months, thanks to the advent of TKI medication [1, 1618]. All current guidelines aim for close patient monitoring with quantitation of disease burden, to identify patients for whom TKI therapy needs to be upgraded to more potent TKI agents [9, 19, 20]. Moreover, mutational studies allow for identification of patients for whom aggressive protocols need to be considered right from the beginning [21].

However, still banding cytogenetic analysis plays an important role in first diagnostics and management of CML [22]. Besides detection of Ph chromosome, complex chromosomal abnormalities can be identified, which may determine the patient as candidate for alternative and more aggressive therapeutic options, sometimes even leading to allogeneic stem cell transplantation [23,24,25].

Acquisition of additional cytogenetic abnormalities, including 5q-, can be one of the markers for clonal evolution, thus warranting patient re-evaluation that could possibly change the disease management plan [11, 26]. While chromosome 5q deletion has good prognostic implication in patients with de-novo myelodysplastic syndrome (MDS), when identified in patients with therapy related or de-novo acute myeloid leukemia, the prognosis is poor [27, 28]. 5q deletion in CML has been reported only rarely in patients yet during therapy with conventional TKI or after stem cell transplantation [13, 14]. Similarly, there have been cases that were initially diagnosed and managed as MDS associated with 5q deletion, who ultimately transformed to Ph + CML while retaining the original 5q deletion in the novel malignant clones [13]. Our patient, who presented with characteristic clinical and hematological features of CML in chronic phase, was initially a healthy individual, suggesting rather that the 5q- was acquired most likely after Ph chromosome appeared in the bone marrow cell clone.


To our knowledge our patient was the first case of Ph + CML with 5q deletion at diagnosis. Therapeutic and prognostic implication of such a presentation would require further evaluation, including close follow-up.

Availability of data and materials

All generated data is included in this article.



Abelson gene 1


Break point cluster region


Complete blood count


Chronic myeloid leukemia


Myelodysplastic syndrome


Philadelphia chromosome


Quantitative polymerase chain reaction


Tyrosine kinase inhibition


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With this writing we would like to acknowledge the efforts by Agha Khan Development Network (AKDN), for the Afghanistan’s first cytogenetic laboratory.



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Authors and Affiliations



AMH and JA-G conceived the idea. AMH, ZAA and JA-G were the major contributor to the writing of the manuscript. EE, MH, AHS and NY collected the laboratory data via integrated laboratory management system (ILMS). AMH and SN diagnosed the case. SN provided the clinical information of the patient. SR, MA, FE, NY and SS performed cytogenetic studies. SN, AMH, ASI, NL and HAM were the major contributors for critically revising the manuscript for important intellectual content. JA-G and AMH have given expert opinion and final approval of the version to be published. All authors read and approved the final manuscript.

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Correspondence to Ahmed Maseh Haidary.

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Haidary, A.M., Ahmed, Z.A., Abdul-Ghafar, J. et al. Philadelphia chromosome positive chronic myeloid leukemia with 5q deletion at diagnosis. Mol Cytogenet 14, 16 (2021).

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